**[GUIDELINES FOR THE USE OF PROTON RADIATION THERAPY IN NATIONAL CANCER
INSTITUTE SPONSORED COOPERATIVE GROUP CLINICAL TRIALS]{.underline}**  

There are potential advantages to patients from proton radiation therapy
(PRT) but substantial concerns persist at present regarding the actual
planning, optimization and execution of PRT in the multi-institutional
setting of co-operative group clinical trials. Therefore, there is a
need for credentialing and quality assurance procedures that are
specific for PRT.

Protons are less tolerant than photons of inadequacies in the planning,
optimization and execution of radiation therapy. This reflects the
nature of the interactions of protons with matter. The guidelines below
are intended to ensure that when PRT is employed in the setting of a
multi-institutional co-operative group clinical trial neither patient
safety nor the study is compromised. The guidelines only specify the
MINIMUM required of any facility that treats with PRT patients
participating in any NCI-supported clinical trial that requires or
allows PRT; they are not to be construed as prescriptive of standards of
care.

**[Guidelines:]{.underline}**

1.  Before treating with PRT any patients participating in a cooperative
    group protocol, an institution must be appropriately credentialed
    for PRT by the QA center designated in the protocol.

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1.  Only passively scattered or actively scattered (wobbling) beams
    shall be employed \[1\].

2.  The IAEA TRS 398 protocol (available at
    <http://www-naweb.iaea.org/nahu/dmrp/pdf_files/CoPV11b.pd> ) shall
    be used for beam calibration \[2\].

3.  All doses shall be expressed as Cobalt Gray Equivalent (CGE, e.g. 70
    CGE) employing a standard RBE of 1.1 with respect to Cobalt-60
    \[3\].

4.  Treatment planning shall be performed on a CT scan obtained with the
    patient in the treatment position. Correlation between the
    institutional 'CT treatment planning system Hounsfield Units' (for
    the specific CT scanners and parameters) and 'relative proton
    stopping power' must be established at each institution and
    demonstrated to the satisfaction of the quality assurance center
    designated in the protocol \[4\]. 

5.  Doses will be specified to volumes using standard nomenclature, i.e.
    GTV, CTV, and PTV. The GTV and CTV shall be identical for protons
    and photons but in specifying the PTV every protocol that allows PRT
    must explicitly address issues unique to PRT such as range
    uncertainties and lateral scatter \[5\].  

6.  Before treating with PRT any patients participating in a cooperative
    group protocol, an institution shall undergo a site-visit by the
    Radiological Physics Center (RPC) for conducting measurements and an
    audit of its proton facility. In addition, the RPC shall conduct
    annual remote monitoring of the proton calibrations as they relate
    to clinical trials in which the facility is participating \[6\].

7.  Every protocol that allows PRT must specify a radiation oncologist
    actively practicing at a proton facility who will be responsible for
    incorporating into that protocol the appropriate dose terminology
    and the specific constraints related to the PTV and OAR \[7\].

***[Rationale:]{.underline}***

1.  *There is substantial clinical experience with passively and
    actively scattered proton beams in the United States while there is
    very limited clinical experience with scanned proton beams. Hence
    approval of the latter for NCI-sponsored protocols will be deferred
    until this approach matures in the US at which time these guidelines
    will be updated.*

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1.  *IAEA TRS 398 will be the recommended protocol by the ICRU in an
    upcoming report and it is based upon a National Institute of
    Standards and Technology (NIST) traceable Cobalt 60 calibration. T
    he difference in calibration between the ICRU recommendations, ICRU
    59, and the IAEA recommendations is quite small, less than 2%,
    though it depends upon the ion chamber used.*

2.  *This RBE and dose specification has been used historically by each
    of the facilities within the U.S., so this will allow for clinical
    continuity of treatment methods and results.*

3.  *The conversion of HU to stopping power ratios determines the energy
    (range) required of the protons and must be performed at each
    institution.  The HU to physical density calibration curve should be
    independently reviewed.*

4.  *The use of the PTV concept is more challenging for protons in that
    it must incorporate the uncertainties in the distal and proximal
    range, which are a treatment field specific requirement.  Currently,
    there is no consensus approach to the use of the PTV concept with
    protons.  It is recommended that the use of the PTV concept be based
    on particular protocol requirements and institutional procedures to
    account for motion of patient and internal organs as well as
    variability in set-up and uncertainties in the proton range.*

5.  *The RPC is funded by the NCI to maintain uniformity and NIST
    traceability of all physical dosimetry in NCI clinical trials, both
    photon and proton. The on-site visit will verify the proton beam
    calibrations and will capture the data needed by the QA center to:*

    -   *assess the accuracy of the CT/ HU to stopping power
        conversion,*

    -   *assess the accuracy of the treatment planning algorithm, and*

    -   *assess the adequacy of patient specific immobilization
        techniques.*

> *Each of these factors will be evaluated in the context of the
> specific protocol requirements.*

1.  *The characteristics of protons are unique enough that they are not
    readily appreciated from the traditional photon experience. Hence,
    special knowledge and experience is required in order to ensure
    patient safety and adequacy of the trial design.*