Non-Homogeneous Tumor Growth and Its Implications for Radiotherapy: A Phenomenological Approach

Abstract

Tumor regrowth and heterogeneity are important clinical parameters during radiotherapy, and the probability of treatment benefit critically depends on the tumor progression pattern in the interval between the fractional irradiation treatments. We propose an analytic, easy-to-use method to take into account clonal subpopulations with different specific growth rates and radiation resistances. The different strain regrowth effects, as described by Gompertz law, require a dose-boost to reproduce the survival probability of the corresponding homogeneous system and for uniform irradiation. However, the estimate of the survival fraction for a tumor with a hypoxic subpopulation is more reliable when there is a slow specific regrowth rate and when the dependence on the oxygen enhancement ratio of radiotherapy is consistently taken into account. The approach is discussed for non-linear two-population dynamics for breast cancer and can be easily generalized to a larger number of components and different tumor phenotypes.

A Novel Radiotherapeutic Approach to Treat Bulky Metastases Even From Cutaneous Squamous Cell Carcinoma: Its Rationale and a Look at the Reliability of the Linear-Quadratic Model to Explain Its Radiobiological Effects

“…However, cell interactions against the background of the host immune system are not fully known and, consequently, not purposely engageable to lead an antitumor response. On the other hand, by adopting an in silico model to explain the interaction (that is, the killing effect) between radiation dose and hypoxic cells, the radical dose to eliminate them all, even after taking into account the time between a fraction and the next one, could be approximately predicted ( 12 ).…”

“…Spatially fractionated RT (SFRT), specifically lattice RT, overcomes such an issue by delivering a highly heterogeneous radiation dose to large targets in order to spare the neighboring organs at risk (OARs) ( 11 ). Such a peculiar dose delivery method could face the typical non-homogeneous tumor growth by selecting the hypoxic regions to be boosted for overcoming their relative radioresistance ( 12 ). In these scenarios, choosing the best dose prescription could be very difficult for the radiation oncologist who must strike a balance between an optimal tumor control probability (TCP) and an acceptable NTCP ( 13 ).…”

Neoadjuvant Stereotactic Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis of the Literature and Ongoing Clinical Trials

“…Moreover, some challenging bulky asymptomatic BMs may also benefit from neoadjuvant or definitive spatially fractionated radiation techniques, which allow for the delivery of non-homogeneously large stereotactic doses while avoiding concerns about an alarming dose-volume effect [ 56 , 57 ]. The SRT’s dose distribution may be adapted to the non-homogeneity of tumor oxygenation, intended to overcome the radioresistant tumor hypoxic sub-volumes while eliciting a useful bystander effect on the under-dosed areas [ 58 , 59 ]. However, at the present time, the usefulness of this approach remains only theoretical, as the current imaging techniques are not able to correctly detect the tumor oxygen landscape.…”

Lattice or Oxygen-Guided Radiotherapy: What If They Converge? Possible Future Directions in the Era of Immunotherapy

“…All the above-mentioned experiences are summarized in Table 1. The inhomogeneous neoangiogenic sprouting that supports the sprawling cancer cells proliferation could generate hypoxic areas due to a non-uniform and deficient oxygen supply for the entire tumor volume [26]. Such hypoxic "islands" are characterized by slow metabolism and, consequently, by some radioresistance [27].…”