Utilization of intensity-modulated radiation therapy and image-guided radiation therapy in pancreatic cancer: is it beneficial?

The recent development of intensity-modulated radiation therapy (IMRT) and improvements in image-guided radiotherapy (IGRT) have provided considerable advances in the utilization of radiation therapy (RT) for the management of pancreatic cancer. IGRT allows for the reduction of treatment volumes, potentially less chance of a marginal miss, and quality assurance of gastrointestinal filling, while IMRT has been shown to reduce both sudden and late side effects compared with 3-dimensional conformal RT. Here, we review published data and provide essential recommendations on the utilization of IMRT and IGRT for the management of patients with pancreatic cancer.

Stereotactic Ablative Radiotherapy (SABR): Impact on the Immune System and Potential for Future Therapeutic Modulation.

Stereotactic ablative radiotherapy (SABR) has been demonstrated to provide excellent local control in several malignancies. Recent reports have suggested that this ablative dose may impact disease outside of the radiated area. Furthermore, these studies have implicated immune modulation as the primary mechanism of disease response outside the irradiated area. More specifically, T-cell stimulation and tumor necrosis factor-α modulation following high dose irradiation have been suggested as the responsible components of this phenomenon. In addition, the "abscopal effect" may play a role in disease response outside of the radiated area. We review the current literature regarding the effects of ablative radiation therapy, the potential for immune modulation from it, and the mechanisms of the distant effects it elicits.

Integral dose conservation in radiotherapy.

Treatment planners frequently modify beam arrangements and use IMRT to improve target dose coverage while satisfying dose constraints on normal tissues. The authors herein analyze the limitations of these strategies and quantitatively assess the extent to which dose can be redistributed within the patient volume. Specifically, the authors hypothesize that (1) the normalized integral dose is constant across concentric shells of normal tissue surrounding the target (normalized to the average integral shell dose), (2) the normalized integral shell dose is constant across plans with different numbers and orientations of beams, and (3) the normalized integral shell dose is constant across plans when reducing the dose to a critical structure. Using the images of seven patients previously irradiated for cancer of brain or prostate cancer and one idealized scenario, competing three-dimensional conformal and IMRT plans were generated using different beam configurations. Within a given plan and for competing plans with a constant mean target dose, the normalized integral doses within concentric "shells" of surrounding normal tissue were quantitatively compared. Within each patient, the normalized integral dose to shells of normal tissue surrounding the target was relatively constant (1). Similarly, for each clinical scenario, the normalized integral dose for a given shell was also relatively constant regardless of the number and orientation of beams (2) or degree of sparing of a critical structure (3). 3D and IMRT planning tools can redistribute, rather than eliminate dose to the surrounding normal tissues (intuitively known by planners). More specifically, dose cannot be moved between shells surrounding the target but only within a shell. This implies that there are limitations in the extent to which a critical structure can be spared based on the location and geometry of the critical structure relative to the target.

Quantifying the dosimetric trade-offs when using intensity-modulated radiotherapy to treat concave targets containing normal tissues.

PURPOSE: To quantitatively assess the relationship between intensity-modulated radiotherapy (IMRT)-driven sparing of dose to normal tissues located "within" concave targets with heterogeneity in dose delivered to the target and redistribution of dose to normal tissue beyond the concavity. METHODS AND MATERIALS: A combination of idealized and real-patient volumes was considered. Multiple IMRT plans were generated with progressive dose restriction to the normal tissue within the concavity. We quantified the impact of such sparing on the heterogeneity of dose within the target tissue itself, and the dose received by normal tissues beyond the concavity. RESULTS: As the dose to the normal tissue concavity region is reduced, the heterogeneity in dose delivered to the target increases in an exponential fashion. Furthermore, there is a rapid increase in redistributed dose to other normal tissue regions, particularly to the other normal tissues immediately adjacent to the outside edges of the concavity. Increasingly restricting dose to these adjacent normal tissue regions resulted in increasing dose to the normal tissue in the concavity and increasing dose heterogeneity in the target volume. CONCLUSIONS: For targets with concavities, there are dosimetric consequences associated with reducing dose to normal tissue located within these concavities. There appears to be a trade-off between the heterogeneity in dose delivered to the target, the mean dose to the concavity, and the redistributed dose to other normal tissues. Understanding the interaction between these dosimetric factors can aid the planner in assessing the feasibility of a desired dose distribution.