Perspectives in radiation oncology

Cancer immunology. Bench to bedside immunotherapy of cancersNima Rezaei (Ed.). Springer-Verlag (2015)

Advances in CSC biology would not only prove useful in the development of targeted drugs but represent a major challenge in the creation of new paradigms of treatment in radiotherapy.

Definition of total tumor volume and prognostic stratifications could be implemented with integration of data upon total number of CSCs, spatial distribution of CSCs, and detection of CSC niches: this information could be integrated in the treatment planning and dose prescription process. Mapping distribution of neural stem cells in human brain led to the observation—in a retrospective cohort of 55 patients affected by glioblastoma—that patients receiving higher doses to the subventricular zone (SVZ) and the subgranular layer (that could act as a reservoir for brain CSCs) experienced a benefit in progressionfree survival [304].

Histopathologic reports, or imaging with radiolabeled antibodies directed to specific CSC markers, could be useful to forecast the likeliness of metastatic spread and, according the ratio of CSCs on total tumor volume, to predict radioresistance: these information could be subsequently applied to determine the correct pattern of care, for example, schedule and timing of associated chemotherapy. Biomolecular profiling on CSCs from pretherapeutic biopsy or postoperative specimens could further drive the choice for altered fractionation schedules or appropriate target therapy, to restore radiosensitivity by pharmacological abrogation of aberrant signaling pathways, concomitant with or prior to radiotherapy. Real-time CSC-specific imaging [305] could be useful to improve feasibility and effectiveness of adaptive radiotherapy.

Moreover, assessment of therapeutic response in neoadjuvant treatments adding CSC-specific imaging could significantly improve the accuracy of restaging [306]. Ion therapy could yield a major benefit in this setting: preclinical data suggest that, in in vitro NSCLC models, protons may be more effective than photons, at the same biologically effective dose, to eradicate CSCs, despite producing equivalent effects in normal bronchial epithelial cells [307]. In a recent publication, carbon ions showed superior biological Efficacy, in terms of lower CSC fraction, as compared to classical photon beam therapy [308].

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