Results Confounded by a Disregard for Basic Dose–Response Radiobiology

Abstract

8. Smits ML, Nijsen JF, van den Bosch MA, in patients with unresectable, chemorefractory liver metastases (HEPAR trial): a phase 1, dose-escalation study. Lancet Oncol. 2012;13:1025-1034. Salem R, Lewandowski RJ, Gates VL, et al. REPLY:We would like to thank Drs. Lam and Smits for their concerns and comments regarding the methodology in our study (1). The aim of our study was to answer the frequently occurring clinical question of whether a patient with low or no 99m Tcmacroaggregated albumin ( 99m Tc-MAA) uptake in metastatic lesions should undergo 90 Y-radioembolization. The observation in our patient cohort with colorectal liver metastasis was that therapy response after 90 Y-radioembolization was independent of the degree of intratumoral 99m Tc-MAA uptake. Consequently, our recommendation to the reader was that "therapy should not be withheld from patients with colorectal liver metastases lacking intratumoral 99m Tc-MAA accumulation" (1).Our results are based on the current body-surface-area model available, taking all the insufficiencies and drawbacks of the surrogate 99m Tc-MAA into account (2). The establishment of dose-response relationships was beyond the scope of our study. Although qualitative Bremsstrahlung or 90 Y-PET imaging may be feasible in clinical routine, one has to admit that a quantitative assessment of dose estimations in normal liver parenchyma in regard to liver-related adverse events and in multiple tumor lesions in both liver lobes is far more difficult (3,4).However, we agree with Drs. Lam and Smits that it would be essential to establish individualized treatment planning on the basis of optimized scout-dose imaging. Besides the technical aspects, such as catheter tip position or injection flow, it is desirable to have an agent that is identical to or that better models the treatment device. The recently introduced 166 Ho-microspheres by Smits et al. (5) may be used for pretherapeutic assessment and treatment evaluation, making them a promising candidate for future application. Nevertheless, we consider flow alterations during the radioembolization process due to the embolization effect to be a significant contributor to variable microsphere distribution in the tumor and liver that cannot be estimated or overcome by any proposed approach.An optimization of dose estimation and individual treatment planning is even more important for further evaluation of the clinical and biologic aspects of the dose-response relationship for different tumor entities, pretreatment with chemotherapeutics, or a combined treatment and sequential lobar treatment versus whole liver treatment (6).An individualized dosimetry concept should improve the efficacy of 90 Y-radioembolization while potentially reducing cases of overtreatment and unnecessary toxicity. To define the method and role of individualized pretreatment planning, a prospective multicenter trial would be needed.Again, we thank Drs. Lam and Smits for their comments and discussion. Results Confounded by a Disregard for Basic Dose-Response Radio...

A review of 3D image-based dosimetry, technical considerations and emerging perspectives in 90Y microsphere therapy

“…This work shows conflicting results with other studies, and many recent letters have discussed these results in detail [59,73,[104][105][106][107]. An important conclusion of these discussions is that in dosimetry comparisons of 90 Y-RE, consideration should be given to the type of microsphere, quantification method, tumour type and the method of response assessment.…”

Yttrium-90 hepatic radioembolization: clinical review and current techniques in interventional radiology and personalized dosimetry

“…However, such studies were often confounded by a lack of radiobiological perspective and mislead less experienced readers. [24][25][26] Others challenge 99m Tc MAA predictive dosimetry based on the physical differences between MAA vs resin or glass microspheres and differences in injected microparticle load. Although these physical differences are undeniably true, the concept often overlooked is that 99m Tc MAA SPECT/CT is meant to depict what the microsphere biodistribution is likely to be and was never intended to exactly replicate the actual microsphere biodistribution.…”

Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres

“…A knowledge gap exists today between institutions which practice predictive dosimetry and others which rely on semi-empirical methods [3]. Readers who are accustomed to semi-empirical therapy planning may struggle to understand the dosimetric concepts discussed in this paper or its relevance to clinical practice.…”

“…Readers who are accustomed to semi-empirical therapy planning may struggle to understand the dosimetric concepts discussed in this paper or its relevance to clinical practice. These readers are encouraged to refer to our recent series of publications explaining concepts in modern predictive dosimetry for 90 Y resin microspheres and common misconceptions [3-6]. …”

“…Where prognostication is of concern, qualitative analysis alone will not suffice [3]. The scientific language of dose-response radiobiology is the radiation absorbed dose expressed in grays (Gy), not the prescribed activity expressed in becquerels (Bq).…”