Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases

doi:10.1016/j.prro.2016.05.004

Practical Radiation Oncology

Volume 6, Issue 6, November–December 2016, Pages e291-e298

https://doi.org/10.1016/j.prro.2016.05.004 Get rights and content

Abstract

Introduction

In 2014, the NRG Oncology Group initiated the first National Cancer Institute-sponsored, phase 1 clinical trial of stereotactic body radiation therapy (SBRT) for the treatment of multiple metastases in multiple organ sites (BR001; NCT02206334). The primary endpoint is to test the safety of SBRT for the treatment of 2 to 4 multiple lesions in several anatomic sites in a multi-institutional setting. Because of the technical challenges inherent to treating multiple lesions as their spatial separation decreases, we present the technical requirements for NRG-BR001 and the rationale for their selection.

Methods and materials

Patients with controlled primary tumors of breast, non-small cell lung, or prostate are eligible if they have 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body. Prescription and organ-at-risk doses were determined by expert consensus. Credentialing requirements include (1) irradiation of the Imaging and Radiation Oncology Core phantom with SBRT, (2) submitting image guided radiation therapy case studies, and (3) planning the benchmark. Guidelines for navigating challenging planning cases including assessing composite dose are discussed.

Results

Dosimetric planning to multiple lesions receiving differing doses (45-50 Gy) and fractionation (3-5) while irradiating the same organs at risk is discussed, particularly for metastases in close proximity (≤ 5 cm). The benchmark case was selected to demonstrate the planning tradeoffs required to satisfy protocol requirements for 2 nearby lesions. Examples of passing benchmark plans exhibited a large variability in plan conformity.

Discussion

NRG-BR001 was developed using expert consensus on multiple issues from the dose fractionation regimen to the minimum image guided radiation therapy guidelines. Credentialing was tied to the task rather than the anatomic site to reduce its burden. Every effort was made to include a variety of delivery methods to reflect current SBRT technology. Although some simplifications were adopted, the successful completion of this trial will inform future designs of both national and institutional trials and would allow immediate clinical adoption of SBRT trials for oligometastases.

Section snippets

Background

Oligometastases defines the proposed clinical state between locoregionally confined cancer and widespread metastases.¹ Cancer patients with few metastases limited in number and distribution could potentially be cured if all visible tumors were ablated with radiation therapy or surgery. With the increasing availability of the technological advances enabling stereotactic body radiation therapy (SBRT),² the use of ablative radiation therapy to treat oligometastases is increasing.³ To date, several

Rationale for technical requirements

Because this is the first National Clinical Trials Network SBRT trial intending to treat patients to multiple anatomic sites, exhaustive technical challenges were discussed and addressed during protocol development. Some of the items that had to be reconciled among the treatment sites included motion management, image guided radiation therapy (IGRT), composite dose calculation, organ-at-risk (OAR) dose constraints (considering variable time courses and fractionation schedules), and positioning

Considerations on selection of appropriate SBRT Doses

Reported phase 2 SBRT studies have typically described patients receiving ablative radiation therapy to a single organ.[11], [12] As such, each target organ has developed a literature of dose volume metrics for acceptable treatment plans and expected toxicity. However, NRG-BR001 is investigating the safety of treating 2 to 4 metastases distributed among 7 extracranial anatomic locations throughout the body (Table 1). To adapt these differing dose-volume metrics for multiorgan stereotactic

SBRT simulation and target delineation

Many challenges are faced when simulating patients for multiorgan ablative radiation therapy. Although immobilization is critical to ensure reproducible setup and minimal intrafraction motion, there is no gold standard, and patient immobilization should always prioritize patient comfort for otherwise longer than typical treatments. The CT scan must include all metastases intended for SBRT to allow for tabulation of composite dose to the OAR. Occasionally, more than 1 treatment position is

Treatment planning challenges for MOSART

Challenges also arise when planning with different ablative dose fractionation schemes in the same patient. In particular, there is no standard guidance on how to assess the contributions to a single OAR from different metastases treated with different fractionation regimens. Also, we acknowledge that clinicians must always balance planning target volume (PTV) coverage against OAR limits to select treatments that they believe will provide the best possible chance of tumor control without OAR

Benchmark credentialing

To aid centers participating in this protocol as well as others adopting multitarget multiorgan SBRT, we developed a benchmark case to serve as a planning tool to familiarize participating institutions with the specific planning goals of the protocol before enrolling/planning their first patient. Feedback regarding plan quality can be given to an institution without the pressure of a patient urgently waiting to begin treatment. Fig 2 depicts the benchmark case for NRG-BR001, consisting of

SBRT treatment planning and evaluation

Previous lung SBRT protocols (eg, RTOG 0236, RTOG 0813) provided general guidelines for dose falloff (eg, dose at 2 cm away from the target [D2cm] and the 50% volume as a ratio of the PTV volume [R50%]). Similar guidelines do not exist for non-lung SBRT; however, because they were developed for targets within lung tissue, it is expected that comparable or superior dose gradients are achievable in higher density organs throughout the rest of the body. Although these guidelines should be followed

Image guidance and radiation dose delivery credentialing for MOSART

Ensuring that SBRT can be delivered safely and accurately to any target in the body is a challenging endeavor, even more so when targeting multiple lesions in the same treatment course; therefore, it was important to establish a mechanism where by the targeting and delivery of SBRT could be validated for each institution prior to patient treatment. As a result, we adapted credentialing from previous RTOG SBRT protocols for a single anatomic site but generalized it to the functional task being

Take-home points

To ensure safe and accurate delivery of ablative radiation therapy to multiple targets in multiple organ sites, credentialing and technical requirements were developed for NRG-BR001 to ensure minimum technical competency without regard to the anatomic site (ie, to test function independent of anatomic site). To acknowledge the technical difficulty of treating targets with high doses with nearby or overlapping OARs, prioritization of prescription doses and OAR constraints were interleaved.

Conclusions

NRG-BR001 is the first National Cancer Institute-supported national protocol to study the safety and feasibility of the treatment of multiple metastases at various anatomic locations. Technical challenges spanning treatment planning and radiation delivery were addressed in developing a generalized SBRT protocol for treatment to any anatomic organ. Although the results of this protocol will provide invaluable data on technical and planning guidelines that will guide the development of future

Acknowledgments

We thank the following individuals for providing their expert opinion during protocol development: Indrin Chetty PhD, Laura Dawson MD, Timothy Solberg PhD, and Fang-Fang Yin PhD.

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Citation Excerpt :
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: Sources of support: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology Statistical and Data Management Center), and U24CA180803 (Imaging and Radiation Oncology Core) from the National Cancer Institute.

: Conflicts of interest: K.A.W. received grants from the National Cancer Institute as a subcontract to the American College of Radiology during the conduct of the study. C.G.R. reports grants and personal fees from Varian, personal fees from Radialogica, personal fees from ViewRay, grants from Elekta, and personal fees from DFINE outside the submitted work. R.D.T. reports grants from Varian Medical Systems, Accuray, Inc, and Elekta Oncology outside the submitted work.

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Special ArticleRationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases

Abstract

Introduction

Methods and materials

Results

Discussion

Section snippets

Background

Rationale for technical requirements

Considerations on selection of appropriate SBRT Doses

SBRT simulation and target delineation

Treatment planning challenges for MOSART

Benchmark credentialing

SBRT treatment planning and evaluation

Image guidance and radiation dose delivery credentialing for MOSART

Take-home points

Conclusions

Acknowledgments

Int J Radiat Oncol Biol Phys

Semin Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Oligometastases

J Clin Oncol

Stereotactic body radiation therapy: The report of AAPM Task Group 101

Med Phys

Special Article
Rationale of technical requirements for NRG-BR001: The first NCI-sponsored trial of SBRT for the treatment of multiple metastases