Improving external beam radiotherapy by combination with internal irradiation

Abstract

The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

MRI-guided radiotherapy of the SK-N-SH neuroblastoma xenograft model using a small animal radiation research platform

“…Robust methods to plan and assess RT efficacy in this preclinical model is vitally important for the evaluation of new therapeutic approaches: for example, protocols that combine RT with chemotherapy and radionuclide therapy. 10 …”

Improved outcome of 131 I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma

“…The potential benefits of combining EBRT and MRT are substantial as the dose limiting organs of the two modalities differ, thus allowing escalation of solid tumour doses without exceeding dose to the limiting organs [4] . This approach is of particular interest in the treatment of neuroendocrine tumours in paediatric patients considering the age of the affected patients and the location of this cancer (frequently adjacent to dose-limiting normal organs such as the kidney and liver) [24] .…”

“…Combined modality EBRT plus MRT for HRNB treatment could prove to be an effective addition to currently available therapeutic options. The distinct advantage of combining different radiation therapy modalities lies in the ability to achieve higher radiation absorbed tumour doses without compromising the dose limiting organs of each individual therapy [4] , [5] . The efficacy of combining EBRT and 131 I-mIBG in the management of malignant phaeochromocytoma and paraganglioma was recently demonstrated by Fishbein and co-workers [6] .…”

“…Several studies have investigated the rationale of combining EBRT and MRT in vitro for glioblastoma and head and neck squamous cell carcinoma [7] , [8] as well as in vivo for breast, colorectal and squamous cell carcinoma models [9] , [10] , [11] , showing an additive effect for the combination of the two treatments when they are given sequentially or concurrently. Additionally, it has been shown that EBRT increases vessel permeability which could increase MRT uptake and distribution within the tumour [4] . The challenge is to define more effective approaches for the combination of EBRT and MRT in the treatment of HRNB while maintaining an acceptable toxicity profile.…”

Glioblastoma multiforme: emerging treatments and stratification markers beyond new drugs

“…It is beyond the scope of this review to discuss all published studies. For a detailed review on RIT, see Zalutsky, 111 Carlsson et al, 110 Seidl 114 and Dietrich 115 . Table 1 summarizes the studies reviewed here.…”