PRACTICE PARAMETER 1 Radiation Oncology Proton Therapy
The American College of Radiology, with more than 30,000 members, is the principal organization of radiologists, radiation oncologists, and clinical medical
physicists in the United States. The College is a nonprofit professional society whose primary purposes are to advance the science of radiology, improve
radiologic services to the patient, study the socioeconomic aspects of the practice of radiology, and encourage continuing education for radiologists, radiation
oncologists, medical physicists, and persons practicing in allied professional fields.
The American College of Radiology will periodically define new practice parameters and technical standards for radiologic practice to help advance the science
of radiology and to improve the quality of service to patients throughout the United States. Existing practice parameters and technical standards will be reviewed
for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.
Each practice parameter and technical standard, representing a policy statement by the College, has undergone a thorough consensus process in which it has been
subjected to extensive review and approval. The practice parameters and technical standards recognize that the safe and effective use of diagnostic and therapeutic
radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice parameter and
technical standard by those entities not providing these services is not authorized.
Revised 2023 (CSC/BOC)*
ACR–ARS PRACTICE PARAMETER FOR THE PERFORMANCE OF PROTON
BEAM RADIATION THERAPY
PREAMBLE
This document is an educational tool designed to assist practitioners in providing appropriate radiologic care for
patients. Practice Parameters and Technical Standards are not inflexible rules or requirements of practice and are not
intended, nor should they be used, to establish a legal standard of care
1
. For these reasons and those set forth below,
the American College of Radiology and our collaborating medical specialty societies caution against the use of these
documents in litigation in which the clinical decisions of a practitioner are called into question.
The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the
practitioner considering all the circumstances presented. Thus, an approach that differs from the guidance in this
document, standing alone, does not necessarily imply that the approach was below the standard of care. To the
contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in this
document when, in the reasonable judgment of the practitioner, such course of action is indicated by variables such
as the condition of the patient, limitations of available resources, or advances in knowledge or technology after
publication of this document. However, a practitioner who employs an approach substantially different from the
guidance in this document may consider documenting in the patient record information sufficient to explain the
approach taken.
The practice of medicine involves the science, and the art of dealing with the prevention, diagnosis, alleviation, and
treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most
appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be
recognized that adherence to the guidance in this document will not assure an accurate diagnosis or a successful
outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on
current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The
purpose of this document is to assist practitioners in achieving this objective.
1
Iowa Medical Society and Iowa Society of Anesthesiologists v. Iowa Board of Nursing 831 N.W.2d 826 (Iowa 2013) Iowa Supreme Court refuses to find that
the ACR Technical Standard for Management of the Use of Radiation in Fluoroscopic Procedures (Revised 2008) sets a national standard for who may perform
fluoroscopic procedures in light of the standard’s stated purpose that ACR standards are educational tools and not intended to establish a legal standard of care.
See also, Stanley v. McCarver, 63 P.3d 1076 (Ariz. App. 2003) where in a concurring opinion the Court stated that “published standards or guidelines of
specialty medical organizations are useful in determining the duty owed or the standard of care applicable in a given situation” even though ACR standards
themselves do not establish the standard of care.
PRACTICE PARAMETER 2 Radiation Oncology Proton Therapy
I. INTRODUCTION
This practice parameter was revised collaboratively by the American College of Radiology (ACR) and the
American Radium Society (ARS).
In 1946, Robert Wilson proposed the clinical use of high-energy protons for the treatment of localized human
tumors, recognizing the energy distribution of charged particles within tissue [1]. Unlike photon treatment, the
charged proton releases most of its energy in the last few millimeters of its range, resulting in a sharp, localized
region of high radiation dose known as Bragg peak. Proton beams of clinical use typically range from 60 MeV–300
MeV energy to treat superficial tumors like skin, eye, head and neck, and breast to deep seated tumors like lung,
prostate, liver, and pancreas [2]. Higher energies can achieve deeper penetration within tissue with a quadratic
relation with range and energy [3]. Spread out Bragg peak width and location can be tailored to deliver a high
radiation dose within the target volume while avoiding irradiation to sensitive normal structures distal to the
intended target [4]. Proton therapy systems traditionally use various synchrotron or cyclotron technologies.
Technologies for proton generation include superconducting synchrocyclotrons and ultracompact synchrotrons.
Proton radiotherapy may be combined with photon beam treatment [5]. Scanned beams capable of delivering
intensity-modulated proton therapy (IMPT) are increasingly being used and have the potential to provide more
conformal dose distribution compared with that of passive scattered proton therapy (PSPT), allowing for the potential
for further reduced normal tissue toxicities [6-9].
The relative role of proton radiotherapy in the context of overall radiation oncology services will require further
investigation, including studies of clinical outcome. On a societal level, the economic costs surrounding the
widespread use of proton radiotherapy may also need to be considered [5]. Increasingly, there are now clinical data
documenting the outcomes of proton radiotherapy across disease sites with many experiences supportive of a
role for proton therapy [10-14].
Proton radiotherapy may permit improved therapeutic ratios with lower doses to sensitive normal structures and
greater dose to target tumor tissues [15]. However, costs of proton treatments are higher than comparable photon
treatments [16-18]. There are now clinical data documenting better outcomes across disease sites in support of
proton therapy [19-24], and such data have provided early evidence for the cost-effectiveness of proton therapy in
select clinical situations and improvement in long-term work productivity [25-28]. On a societal level, the
economic cost-effectiveness surrounding the widespread adoption of proton radiotherapy should be further
investigated [2,5,29,30].
As of 2022, there are 39 proton centers in the United States, a number rapidly growing with increased opening of
single-gantry options [31]. Approximately half of these centers have opened since 2017. This practice parameter is
developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or
other patients with conditions in which radiation therapy is indicated. It addresses clinical implementation of proton
radiation therapy, including personnel qualifications, quality assurance (QA) standards, indications, and suggested
documentation. This practice parameter is not meant to assess the relative clinical indication of proton radiotherapy
compared with other forms of radiotherapy but to focus on the best practices required to deliver proton therapy safely
and effectively when clinically indicated. It also supplements the ACR–ASTRO Practice Parameter for Radiation
Oncology, the ACR–AAPM Technical Standard for the Performance of Radiation Oncology Physics for External-
Beam Therapy, the ACR–ASTRO Practice Parameter for Image-Guided Radiation Therapy (IGRT), and the ACR–
AAPM Technical Standard for the Performance of Proton Beam Radiation Therapy [32-35].
A literature search was performed to identify published articles regarding clinical outcomes, reviews, QA
methodologies, and guidelines and standards for proton radiation therapy. Selected articles are referenced in the text.
Many of the following recommendations are based on firsthand experiences of multiple clinical authorities who
employ proton therapy and peer reviewed by experts at different practicing institutions.
II. QUALIFICATIONS AND RESPONSIBILITIES OF PERSONNEL
See the ACR–ASTRO Practice Parameter for Radiation Oncology in which qualifications, credentialing, professional
relationships, and development are outlined [32].
PRACTICE PARAMETER 3 Radiation Oncology Proton Therapy
A. Chief Medical Officer or Medical Director
The Chief Medical Officer or Medical Director of Proton Therapy (or Radiation Oncology) is responsible for
ensuring that there is an appropriate training and credentialing program for the radiation oncologists, physicists,
dosimetrists, midlevel providers, nurses, and radiation therapists. A QA and performance improvement (PI) programs
should be developed for continuing quality improvement (CQI) as described in the ACR–ASTRO Practice Parameter
for Radiation Oncology [32]. It is the leadership’s responsibility to respond to identified problems and coordinate
with the Qualified Medical Physicist(s) in proton therapy to ensure that the corrective actions are performed, and a
QA process evaluates the effectiveness of the corrective actions.
B. Radiation Oncologist
The training requirements of the radiation oncologist should conform to the qualifications and certification as
outlined in the ACR–ASTRO Practice Parameter for Radiation Oncology [32]. Because this training does not
currently specify proton therapy, specific training in proton therapy should be obtained before performing any such
procedures.
The responsibilities of the radiation oncologist should be clearly defined and should include the following:
1. The radiation oncologist manages the overall disease-specific treatment regimen, including careful
evaluation of disease stage, assessment of comorbidities and previous treatments, thorough exploration of
various treatment options, ample and understandable discussion with patients regarding the impact of
treatment, including benefits and potential harm, knowledgeable conduct of proton therapy as outlined
below, and prudent follow-up after treatment.
2. The radiation oncologist determines and recommends a proper patient positioning method (with
sedation as indicated) with attention to disease-specific targeting concerns, patient-specific capabilities
(eg, arm position in arthritic patients, degree of recumbency in patients with severe chronic obstructive
pulmonary disease), patient comfort, stability of setup, and accommodation of devices accounting for
organ motion (eg, gating equipment) required for optimal targeting of the proton treatment.
3. The radiation oncologist determines and recommends a procedure to account for inherent organ motion
(eg, breathing movement) for targets that are significantly influenced by such motion (eg, lung and liver
tumors) as they relate to and integrate with the accurate delivery of proton therapy. This activity may
include implementation of a variety of methods, such as respiratory gating, tumor tracking, organ motion
dampening, additional imaging, dosimetric modification of target volumes, or patient- directed methods
(such as active breath holding).
4. The radiation oncologist is responsible for the supervision of the patient’s treatment simulation using
appropriate imaging methods. The radiation oncologist must be aware of the spatial accuracy and
precision of the simulation modality as well as of the proton therapy delivery mechanism. Steps must be
taken to ensure that all aspects of simulation, including positioning and immobilization, are properly carried
out.
5. After the planning images have been acquired, they will be transferred to the treatment-planning
computer. Subsequently, the radiation oncologist contours the outline of the targets of interest. Normal
organ structures can be contoured by the physicist, dosimetrist, anatomist, or physician and ultimately
reviewed by the responsible radiation oncologist. Images from various platforms known to be useful for
the specific disease treated should be registered with the planning data set in the image fusion process,
which may serve to aid in defining target volumes. Incorporating information from all relevant imaging
studies, the radiation oncologist coordinates the design of the target volumes and confirms that relevant
normal tissues adjacent to and near the targets are identified and contoured. It should be noted that,
because of the spatial dosimetry of the proton beam, particular consideration must be given to the distal
and lateral edges, in as much as the sharp dose gradient of the beam risks underdosing of the target unless
adequate margins are included within the treated volume. Radiobiological effects on normal tissues at the
distal edge of the target must also be taken into careful consideration, especially when the distal edge is
PRACTICE PARAMETER 4 Radiation Oncology Proton Therapy
near a critical structure.
6. The radiation oncologist conveys case-specific expectations for prescribing the radiation dose to the target
volume and sets limits on dose to adjacent normal tissue. It may be required that certain normal tissues
be tracked under image-guidance just as with the tumor target(s). Participating in the iterative process
of plan development, the radiation oncologist approves the final treatment plan in collaboration with a
medical physicist and dosimetrist.
7. After obtaining informed consent for the proton treatment, the radiation oncologist supervises the actual
treatment process. The conduct of all members of the treatment team will be under the supervision of the
radiation oncologist. The radiation oncologist will be responsible for deciding the acceptable or
unacceptable day-to-day variations in the treatment setup.
8. The radiation oncologist participates in the QA processes, such as approval of proton therapy
assessments, in order to ensure that the intended treatment is being delivered in the prescribed
fashion.
C. Qualified Medical Physicist
The training requirements of the Qualified Medical Physicist should conform to the qualifications and certification as
outlined in the ACR–ASTRO Practice Parameter for Radiation Oncology [32].
In addition, the Qualified Medical Physicist must meet any qualifications imposed by the state and/or local
radiation control agency to practice radiation oncology physics and/or to provide oversight of the establishment and
conduct of the physics quality management program.
The qualifications of a Qualified Medical Physicist and subsequent delineation of clinical privileges must be set
forth in a job description and/or through the medical staff membership process in the appropriate category. Details
regarding the qualifications and responsibilities of the Qualified Medical Physicist for proton therapy are
enumerated in the ACR–AAPM Technical Standard for the Performance of Proton Beam Radiation Therapy [33].
The proton therapy facility must have a process to review the credentials of the qualified medical physicist(s) who are
providing proton clinical physics services especially in beam delivery technology such as scattered beam and scanning
beam techniques. Additionally, the medical physicists should have knowledge of imaging, dose calculation (Hounsfield
Unit (HU), electron density, stopping power), optimization techniques and treatment planning system (TPS) dose
calculations engine. Physicists should also be trained in proton-specific imaging modalities for pretreatment and
posttreatment imaging techniques. A strong understanding of the motion management system is critical as provided in
the American Association of Physicists in Medicine (AAPM) TG-290 [36].
D. Medical Dosimetrist
The responsibilities of the medical dosimetrist or otherwise designated treatment planner should be clearly
defined and should include the following:
1. Satisfactory understanding of anatomy, essential to contouring clearly discernible critical normal structures.
Ensuring proper orientation of volumetric patient image data on the radiation treatment planning (RTP) system.
2. Designing and generating the treatment plan under the direction of the radiation oncologist and medical
physicist.
3. Generating all technical documentation required to implement the proton therapy treatment plan.
4. Being available for the first treatment and assisting with verification for subsequent treatments as
necessary.
5. Knowledge of the motion management system to mitigate interplay effect
PRACTICE PARAMETER 5 Radiation Oncology Proton Therapy
E. Radiation Therapist
The responsibilities of the radiation therapist should be clearly defined and should include the following:
1. Understanding the proper use of the patient immobilization/repositioning system and fabricating and
understanding the proper use of devices for proton therapy.
2. Under the supervision of the radiation oncologist and medical physicist, performing initial (planning)
simulation of the patient and generating the medical imaging data appropriate for the RTP system.
3. Implementing the proton therapy treatment plan under the supervision of the radiation oncologist and
the medical physicist or of the medical dosimetrist under the direction of the medical physicist.
4. Acquiring periodic verification images for review by the radiation oncologist.
5. Performing periodic evaluation of the stability and ongoing reproducibility of the
immobilization/repositioning system and reporting inconsistencies immediately to the radiation
oncologist and the medical physicist.
6. Clear understanding of the motion management system operation
F. Continuing Medical Education
Continuing medical education programs should include radiation oncologists, medical physicists, medical
dosimetrists, and radiation therapists.
The continuing education of the physician and Qualified Medical Physicist should be in accordance with the ACR
Practice Parameter for Continuing Medical Education [37].
III. STANDARD CLINICAL INDICATIONS AND METHODOLOGIES OF TREATMENT
MANAGEMENT
Proton therapy has been used to treat patients across a spectrum of malignancies and benign diseases for which
radiation therapy is indicated. Proton radiotherapy may be seen as both a biologic and a technological option for
the delivery of radiation treatment [38].
The practicing clinician should prescribe radiation therapy, whether photon- or proton-based, in accordance with the
principles enumerated within the ACR–ASTRO Practice Parameter for Radiation Oncology, the ACR–ASTRO
Practice Parameter for Communication: Radiation Oncology, the ACR Code of Ethics, and the AMA Code of
Medical Ethics. These guidelines for professional conduct hold that the welfare of the patient is paramount because
the radiation oncologist makes recommendations for cost-effective treatment [32,39-41].
In this context, the decision to include proton therapy as a component of the patient’s radiation treatment plan
should be discussed with the patient and that discussion should also include other treatment options along with their
relative merits and potential risks. A summary of the consultation should be communicated to the referring physician
and to other physicians involved in the care of the patient.
A. Central Nervous System Brain
1. Rationale:
The application of proton therapy to treat sites within the brain is primarily to reduce radiation-associated
potential adverse effects from reduction or avoidance of collateral radiation to structures such as uninvolved
brain parenchyma [42], brainstem, eyes, lacrimal glands, pituitary, hippocampus [43], and cochleae [44].
Proton therapy may also enable safer radiation dose escalation compared to conventional photon-based
PRACTICE PARAMETER 6 Radiation Oncology Proton Therapy
approaches.
Treatment of intracranial targets is particularly attractive for proton therapy for both clinical and dosimetric
reasons. Clinically, there is a concern that additional surrounding normal tissue, primarily that of t h e
brain, is radiation sensitive, and potential side effects may cause significant detriment to long-term cognition
and quality of life [45]. In regard to treatment setup and planning, the cranium can be irradiated with
greater accuracy because of both reproducible immobilization and greater precision in targeting small
volumes. These factors reduce the amount of collateral normal tissue irradiation.
2. Immobilization and Simulation:
The use of a thermoplastic masks with a customized occipital cushion is standard. Thicker plastic meshes
that provide greater rigidity and less opportunity for patient movement may be preferred [46]; bite blocks
should also be considered. Treatment of targets near or involving the base of skull should use a mask that
encompasses the cranium, neck, and shoulders. Noninvasive cranial frames used for stereotactic treatments
can be used to improve precision through reproducibility of setup and are particularly preferred for small
intracranial targets of ≤2 cm in diameter [47].
3. Treatment Planning:
Depending on location, volume, and dose, multiple fields are typically desired to optimally spare normal
tissues and to spread out end-of-range uncertainty of the relative radiobiologic effectiveness (RBE) at the
distal edge of the target. Avoidance of beams traversing the mastoid air cells and sphenoid/maxillary sinuses
is generally preferred to reduce beam uncertainty from heterogeneous attenuation. Vertex fields that are
often avoided in photon planning because of concerns of beam exiting into the body [48] are less of a
concern with proton therapy and often create a more robust plan with less beam uncertainty by avoiding
passage through mixed tissues with heterogeneous radiologic densities. Because of end-of-range
uncertainties inherent with proton therapy today, it is preferred to avoid beams that end at an interface
with a critical structure such as the optic pathway or brainstem, especially if prescription dose approaches
normal tissue dose tolerance.
B. Spine or Paraspinal Site
1. Rationale:
The anatomic location of spinal and paraspinal tumors that require radiation therapy makes them ideal
candidates for proton therapy. The entrance dose, although less than that of X-rays, is often of little
consequence when treating tumors in this location. The physics advantage of protons, compared to X-rays,
is that they stop abruptly, which is particularly useful in superficial targets such as spinal and paraspinal
targets. Depending on the exact location in the patient, using protons can significantly decrease dose to
thyroid, heart, lungs, esophagus, spinal cord, kidneys, bowel, bone marrow, and/or reproductive organs.
2. Immobilization and Simulation:
Immobilization and simulation are dependent primarily on two factors—patient comfort and the treatment
table itself. Patients can be simulated supine or prone. A variety of immobilization devices can be used
with the goal of patient comfort and reproducibility during daily treatments. These treatment devices
should be “compatible” with proton therapy because the density of material traversed by the proton beam
can impact range and robustness. This is much less of an issue in X-ray–based treatments. Decubitus
positions are difficult to reproduce with high accuracy and should be used in only select circumstances.
The treatment table may drive patient position in some situations. Some proton centers have treatment
tables that have their base built into the treatment floor itself. As a result, there is an inferior limit to how
low a patient can be treated with a posterior-anterior (PA) beam because the gantry may not be able to
clear inferiorly. This lower limit, relative to the patient, is raised for taller patients. In centers with
robotic patient positioning systems (PPS), this is less of an issue, although the treatment “knuckle” of
the treatment couch may interfere with a PA beam angle. This can be mitigated if the couch is “dual
elbowed,” but some PPS are “single elbowed.” Understanding the limitations of the treatment couch or PPS
is critical for all members of the treatment team. For centers with such technical limitations alternative
simulation approaches may include either simulating patients prone or in the “feet first” position. Prone
positioning allows for a PA beam at the zero-degree gantry angle, avoiding the possibility of gantry-table
PRACTICE PARAMETER 7 Radiation Oncology Proton Therapy
collisions. Simulating patients in the “feet first” position allows planning to move the treatment isocenter
superior relative to the treatment couch.
3. Treatment Planning:
PA-weighted beams are ideal for multiple reasons. As described in the rationale section, the physical
properties of protons (measurable entrance dose but no significant exit dose) lend themselves well to
spinal and paraspinal targets. Because skin dose can be higher for protons when a more limited number
of beams are used for proton therapy relative to photon therapy, especially in scattering-based systems,
slightly obliqued beams may be ideal, especially for high treatment doses, to reduce the risk of skin
toxicity. Many patients with disease in the spine or paraspinal areas have prior surgical procedures. If
hardware was placed, its specifications, namely, information such as material and density, must be obtained.
This may require speaking directly with the surgical team and/or the manufacturer of the hardware.
Ideally, this information is obtained before the patient is seen for consult because this may impact
whether the patient is optimally treated with proton therapy from a physics perspective. The use of carbon
fiber spinal hardware, which creates minimal artifacts and back scatter, is increasingly being employed and
available in many medical centers [49]. If the use of proton therapy for a spinal or paraspinal tumor is
anticipated, the treating radiation oncologist can communicate directly with the operating spine surgeon to
consider using carbon fiber hardware, if available, before the operation.
C. Eye
1. Rationale:
Proton therapy is used for ocular tumors for several reasons: (1) very high doses per fraction are used,
which renders maximal avoidance of collateral normal tissue irradiation of great importance; (2) the eye is
a small organ with multiple radiation-sensitive structures, such that unnecessary radiation spillage should
be minimized; (3) the tumors may be large relative to the size of the eye, maximizing importance of
sparing of the remainder of the eye to maximally preserve vision; if feasible [50]; and (4) the superficial
location of these tumors is ideal for protons to limit dose to deeper tissues.
2. Special Considerations:
In general, a special beamline with low energy may be used for this treatment. The treatment of ocular
tumors requires close collaboration between the ophthalmologist and radiation oncologist. In addition,
specialized equipment may be required beyond the standard proton facility arrangement such that not every
proton facility will be equipped to optimally deliver treatment for ocular tumors. Commonly, the
ophthalmologist will guide patient selection with tumor/target definition through techniques such as
funduscopic examination, fluorescein angiogram, ultrasound, and direct tumor measurements
intraoperatively. Most commonly but not imperatively, radio-opaque fiducial markers are sutured to the
sclera and used as references for tumor definition [51]. Other alternative approaches have been devised when
special eye line is not available [52].
3. Immobilization and Simulation:
Typically, a thermoplastic mask or similar device is used for positioning of the head; an additional device
may be used for the maxillary teeth (eg, bite block) to help with positioning and stability. The
thermoplastic mask is trimmed over one or both eyes to allow direct visualization of the eye by the
treatment team.
During simulation, patients’ position must be reproducible and comfortable enough for the patient to
remain in this position throughout the treatment. The patient will visually focus on a particular spot
during simulation and treatment to help maintain eye position. The optimal gaze angle (direction in
which the patient’s gaze is focused) is vital and must be determined before treatment.
Depending on the treatment technique and isodose planning system used, the images obtained during
simulation may either be orthogonal kilovoltage radiographs or may be obtained with volumetric
acquisition using CT imaging that are increasingly available on proton systems [53]. For the volumetric
acquisition, typically very thin slice thickness images are obtained through the orbits. The fiducial markers
and lid retraction devices make volumetric imaging more difficult because of the artifact from those devices.
PRACTICE PARAMETER 8 Radiation Oncology Proton Therapy
4. Treatment Planning:
Treatment planning for ocular tumors has been most frequently performed with a treatment planning
algorithm and software system developed specifically for treatment of ocular tumors. This requires
multiple measurements that are obtained by the ophthalmologist, both from clinical examination and from
surgical evaluation at the time of fiducial clip placement. This technique primarily uses a single anterior
beam in which the gaze angle is adjusted to maximally avoid treatment through the limbus, ciliary body,
cornea, lens, macula, and optic disc. To a lesser extent, beam selection is selected to also avoid unnecessary
lacrimal gland, eyelid, and eyelash irradiation. An option of volumetric technique can be used in which
information from ophthalmologic examination, preclip imaging, and a treatment planning CT and/or MRI
scan are used to create a true 3-D treatment plan. With this technique, typically two–three beams are used,
potentially with lateral, superior, or inferior fields that also avoid the radiation sensitive anterior eye
structures and eyelids.
5. Treatment:
Similar to simulation, the eye position should be fixed or monitored and tracked during treatment, typically
using a camera system mounted on or near the beamline. Depending on the treatment technique, lid
retraction may be used to minimize collateral irradiation to the eyelids and eyelashes. If used, the eye
should be anesthetized (eg, proparacaine eye drops), and a standard eyelid speculum can be used for
retraction.
D. Head and Neck
1. Rationale:
There are many radiation-sensitive critical normal structures in the head and neck region that impact
quality of life during and after treatment when exposed to radiation or chemoradiation during curative
cancer treatment [54]. Proton therapy is used to reduce the dose to those structures, including optic nerves,
optic chiasm, pituitary gland, brain, brainstem, spinal cord, taste buds, salivary glands, pharyngeal
constrictor muscles, oral cavity, larynx, and the emetogenic sites in the posterior fossa in order to reduce
complications and improve patients’ quality of life during and after treatment [22,55-57]. Proton therapy has
enhanced biological effects that can improve the clinical outcomes on individual tumors [58-62]. The
clinical development of multifield optimization associated with IMPT has rapidly established proton
therapy as a standard treatment option for patients with head and neck malignancies in the primary,
adjuvant, and reirradiation settings. A Phase II/III multi-institution randomized trial of IMPT versus IMRT
for patients with advanced stage oropharyngeal tumors has recently completed accrual [8,22,58,60,63-66].
2. Immobilization and Simulation:
Patients are typically treated in the supine position, which must be reproducible and comfortable enough
for the patient to tolerate it throughout the treatment. Typically, a thermoplastic mask or similar device is
use for positioning of the head; an additional device may be used for the maxillary teeth (eg, bite block or
dental mold, ie, stent) [67,68] to help with overall positioning, stability, and tongue position. If posterior
oblique beams are to be used, a frame should be used that encompasses the head, neck, and shoulders with
a curving surface laterally (typically avoid thick edges, which may cause issues with dose calculation). An
additional vacuum-lock bag or foam mold for the upper thorax and neck may be useful for reproducibility,
especially for patients receiving treatment to cervical nodes. This is important because the head can be
more easily immobilized in a reproducible fashion than the neck.
Images should be obtained during simulation with volumetric acquisition using a CT scan. For the
volumetric acquisition, typically thin-slice images are obtained through the head and neck. If there is
significant metal in or near the treatment volume, additional imaging (eg, megavoltage CT scan) or CT
scanner metal artifact reduction software may be useful to help define the normal anatomy.
3. Treatment Planning:
Low energies are required for treatment of superficial structures in the head and neck. This may require
the use of a range shift with water equivalent thickness (WET) [3] to achieve the appropriate range [69].
There may be metallic objects within the treatment volume. These may include hardware for bone
PRACTICE PARAMETER 9 Radiation Oncology Proton Therapy
stabilization placed at surgery (eg, mandibular plate) but more frequently are dental hardware. When
possible, treatment beams should avoid traversing through the dense materials because of the added
attenuation, scatter, and dosimetric uncertainty. If dental hardware cannot be avoided within treatment
fields, in some cases it may be better to recommend replacement of amalgam fillings with composite resin
or ceramic materials. If there is dental or surgical hardware, the relevant physics information (density) must
be obtained. This may require speaking directly with the dentist, surgical team, and/or the manufacturer of
the hardware. Ideally, this information is obtained before the patient is seen for consultation because this
may impact whether the patient is optimally treated with proton therapy from a physics perspective.
Heterogeneity and abrupt changes in density of material along the beam path will create some beam
attenuation and dose deposition uncertainty. Thus, avoidance of the mastoid air cells and paranasal
sinuses is generally preferred. Additional imaging may be required during treatment to evaluate the
air/fluid fill within the sinuses. Because of end-range uncertainties inherent with proton therapy, it is
preferable to avoid beams that end at an interface with a critical structure such as the optic pathway or
brainstem, especially if prescription dose approaches normal tissue dose tolerance [70]. For certain
target volumes, such as those intended to treat bilateral cervical nodes, pencil beam scanning may offer
the optimal balance of conformality and homogeneity.
E. Chest—Breast/Chest Wall
1. Rationale:
There have been several recent reports highlighting the significant risk of major coronary events after
even low-dose radiation exposure to the heart associated with prior photon-based radiotherapy to the breast
and thorax [71-73]. Protons can allow for significant dose reduction to the heart while allowing for
equivalent or superior coverage to the regions at risk, including internal mammary nodes. Protons are
therefore an attractive option for these patients [74]. The dosimetric advantages of proton therapy may allow
for fewer cardiac complications and lower rates of radiation pneumonitis and secondary malignancies
relative to photon therapy [75]. Proton therapy may also have particular dosimetric advantages in the
postmastectomy setting [76] and for patients with synchronous bilateral breast cancers [77]. Proton therapy
may be the most optimal treatment modality for patients with recurrent or new primary breast cancer who
received prior radiation, with a recent large institutional series demonstrating excellent locoregional control
and few high-grade toxicities with proton reirradiation [78]. Prospective studies have demonstrated
excellent local control and good cosmesis with proton therapy for partial breast irradiation [79]and high rates
of disease control and low rates of toxicities with proton therapy for regional nodal irradiation[74].
2. Immobilization and Simulation:
Reproducible neck, shoulder, and torso immobilization are of critical importance with proton therapy;
immobilization devices such as a vacuum bag body mold are helpful to immobilize the patient from above
the head to the lower scapular area, and neck immobilization can also be achieved with the vacuum bag or
with a dedicated headrest. The most common patient treatment position is supine, with the patient’s
ipsilateral arm or bilateral arms up and their hand on top of their head or holding hand grips on an arm
shuttle or breast board. Immobilization considerations that can maximize the avoidance of normal tissue
irradiation may include turning the patient’s head to the contralateral side with their chin extended.
Common patient position comfort measures such as a large knee sponge can improve patient tolerance to
setup.
3. Treatment Planning:
Depending on the patient’s anatomy, one or two enface fields are typically used for breast/chest wall
treatment. Breast/chest wall tissues are defined as the target volume, often with the assistance of radio-
opaque wires placed on the skin surface during simulation and generally exclude the ribs and intercostal
muscle to avoid excessive dose to the lungs. Target volume can be trimmed off of the skin (usually
by a few millimeters) in order to reduce skin dose and consequent reaction. Dosage to heart and esophagus
should be kept as low as possible to minimize toxicities to these organs at risk. Metals and artifacts from
implants/tissue expanders must be contoured and overridden with density overrides and taken into account
during planning. A randomized phase III clinical trial comparing protons and photons for locally advanced
breast comprehensive nodal irradiation is currently nearing accrual completion [80].
PRACTICE PARAMETER 10 Radiation Oncology Proton Therapy
F. Chest—Lung, Intrathoracic Sites
1. Rationale:
Intrathoracic malignancies, including non–small-cell lung cancer, esophageal cancer, thymic tumors, and
mesothelioma, present a significant clinical challenge from a radiotherapeutic standpoint because
intrathoracic progression is a dominant pattern of failure. Because of the fact that these tumors are in close
proximity to radiosensitive vital organs and other critical structures, such as the heart, lungs, esophagus, and
spinal cord, protons offer a dosimetric advantage by allowing dose to be delivered to the target while
minimizing collateral dose exposure to these neighboring critical structures. Additionally, in the case of non–
small-cell lung cancer, in which dose escalation with photons was proven to be unsuccessful ( largely related
to toxicity from dose to normal tissues) [81] despite suboptimal control rates with standard radiation dosing,
protons may allow for safe escalation of tumor dose in a subset of patients [82]. A single-institution study
has shown improved dosimetric conformality of IMPT associated with reduced adverse events from heart,
lung, esophagus, and patient general fatigue when compared with PSPT [7]. Protons have also been used for
reirradiation of recurrent lung cancer after prior concurrent chemoradiation, including in multicenter
prospective studies [83,84], with encouraging outcomes [85-88]. In the setting of non–small-cell lung cancer,
a meta-analysis suggested improved local control and reduced toxicity with proton versus photon
hypofractionation for early stage disease [89], and a population-based study suggested improved survival
with proton versus photon chemoradiation for locally advanced disease [19]. A phase III randomized trial
comparing overall survival for proton versus photon chemoradiation conducted through NRG Oncology is
approaching accrual completion [90].
In the setting of esophageal cancer, a recent prospective randomized trial showed significant reduction of total
toxicity burden, a decrease in hospital stays, and fewer cardiac adverse events with proton therapy [21]. In
thymoma, the spare of the cardiac structures is optimized using proton beam therapy, which can lead to fewer
toxicities and optimized treatment outcomes [91]. Additionally, in thymoma, in which life expectancy is
near normal after complete surgical resection in the absence of local failure, protons represent an attractive
option to deliver a radiation dose to the surgical bed while minimizing the risk of late radiation-induced
cardiac injury [91].
In the setting of mesothelioma, in which a complicated “rind-like” dose distribution must be delivered to
a large volume of the hemithorax, often after surgical resection, protons allow for delivery of this dose
without a significant dose being delivered to the contralateral lung, along with reduction in doses to the
heart and upper gastrointestinal structures [92].
2. Immobilization and Simulation:
The arms should generally be positioned above the patient’s head, commonly with use of a wing board
with hand grips and a plastic headrest. These are often the only devices routinely used for immobilization.
Occasionally, padded sponges or equivalents can be used to support the elbows and knees.
3. Treatment Planning:
In general, multiple fields should be used to optimize conformality and robustness. For the best
accountability of internal organ and target motion, 4-D scanning during simulation should be used. Beams
should be chosen to minimize collateral radiation dose to the lung, heart, esophagus, and spinal cord. IMPT
can allow significant dosimetric benefits over passive scattering proton therapy, which can directly translate
to fewer treatment-related toxicities and improved survival [7]. Motion management is more critical,
however, for IMPT than passive scattering. Motion management such as respiratory gating, abdominal
compression, and active breathing coordination may be considered during simulation if excessive tumor
motion (>5-10 mm) is noted [93]. Volumetric or layer repainting might be used to mitigate tumor motion
interplay effects if pencil beam scanning is to be used. Target volume can be defined in all phases from the
breathing cycle, and the final dose calculation should be performed on the average scan. Proton beam is
very sensitive to density change in the beam path when treating intrathoracic cancers. It is strongly
recommended that repeat simulations during weeks 1 and 2 and weeks 4 and 5 in a six-week course of
proton beam therapy are performed to evaluated any possible anatomic changes and need for adaptive
planning, which could be indicated in as high as 29% of patients [94]. Scheduled replanning best optimizes
PRACTICE PARAMETER 11 Radiation Oncology Proton Therapy
accounting for anatomical changes and may lead to reductions in toxicities and improvements in survival,
with a recent preimmunotherapy prospective trial showing that regular replanning for locally advanced non-
small cell lung cancer can achieve a five-year overall survival of 59%[95].
G. Abdomen—Stomach, Pancreas
1. Rationale:
Radiation therapy for pancreatic cancers delivered in the postoperative or definitive setting, particularly
when combined with concurrent chemotherapy, is often associated with severe fatigue and gastrointestinal
(GI) toxicities, such as nausea, vomiting, diarrhea, abdominal discomfort, and anorexia. The application
of proton therapy for pancreatic cancers is to reduce these GI toxicities that are primarily related to radiation
dose to the stomach, duodenum (especially, in the setting of unresected tumors), and small bowel. A
potential to concurrently combine radiation therapy with more aggressive regimens of chemotherapy (eg,
gemcitabine, nab-paclitaxel, the FOLFIRINOX chemotherapy regimen) using proton therapy may also
exist. In the setting of borderline resectable or locally advanced pancreatic cancers, proton therapy may
also allow for safer dose escalation [96].
2. Immobilization and Simulation:
4-D motion assessment during simulation is necessary to account for stomach, liver, small bowel, large
bowel, and kidney motion. In the definitive treatment of pancreatic tumors, accounting for the tumor target
motion is also important. To minimize the uncertainty of stomach content filling and to maximize the
distance between the stomach and tumor target(s), simulation with an empty stomach is preferred . For
intact tumors, consideration of fiducial marker placement within the tumor should be made for optimal
image-guided therapy, particularly in dose escalation and/or hypofractionated settings. Additionally, for
these tumors, motion management strategies such as abdominal compression, breath-hold, or respiratory
gating should be considered for tumors with >5–10 mm of movement, depending on proton therapy
technique.
3. Treatment Planning:
In the postoperative setting, two–three beams are typically used and arranged to minimize the dose to the
aforementioned GI organs-at-risk (OAR) and minimize beam paths through areas of high uncertainty due
to gas or filling content. A posterior beam delivered in between the kidneys is often the most robust beam
and should always be considered as a beam angle unless the goal of treatment is to avoid the spinal cord in
the setting of reirradiation. Additional beams through the right lateral, anterior oblique, or posterior
oblique angles are often used because the target volumes often include right-sided (porta hepatic,
portocaval) nodes and entrance through the stomach and descending colon; organs prone to interfractional
uncertainty due to variable content filling or gas can be minimized. Similar beam arrangements may be
used for patients with borderline resectable or unresectable tumors, but because the duodenum is also an
important OAR that must be respected, consideration of additional beam angles anteriorly and left laterally
may be made. However, caution must still be exercised when delivering dose to the duodenum for tumors
in the pancreatic head given the close proximity/abutment of these tumors to the duodenum and the
range uncertainty that must be taken into account. This issue is particularly important for dose
escalation strategies.
H. Abdomen—Liver
1. Rationale:
Normal liver tissue is highly radiosensitive to low doses of radiation, especially in cirrhotic livers that
have inherent dysfunction from chronic liver damage. Radiation-related hepatotoxicity is a significant
complication when irradiating liver tumors because no treatment other than supportive care currently exists
to treat this complication that may be fatal. The use of proton therapy for liver cancers therefore is
appealing to reduce dose to normal (uninvolved) liver tissue and to minimize the risk of radiation-
related hepatotoxicity, particularly when treating patients with compromised liver function or with dose
escalation [24]. In addition, reduced dose to surrounding GI organs such as the stomach, duodenum, kidney,
and bowel may also result in reduced radiation-related GI toxicities. Proton therapy for liver cancers has
PRACTICE PARAMETER 12 Radiation Oncology Proton Therapy
often been applied in the hypofractionated setting [97,98].
2. Immobilization and Simulation:
To account for liver and tumor motion, simulation with 4-D assessment is critical to deliver the most
accurate and robust treatment plan. Motion management strategies such as abdominal compression, breath-
hold, or respiratory gating are essential to minimize uncertainty and the interplay effect when tumor motion
is >5 to 10 mm, depending on the proton therapy technique being used. Fiducial marker placement is often
important to evaluate the tumor motion on 4-D assessment as well as provide guidance for on-board imaging
verification. To minimize the uncertainty of stomach content filling, simulation with an empty stomach is
preferred. The use of intravenous (IV) iodinated contrast is important when simulating liver tumors because
these tumors are often not well visualized on noncontrast CT images. It is highly encouraged to use
multiphase (arterial, venous, delayed) contrast-enhanced images for primary liver tumors (hepatocellular
carcinoma, intrahepatic cholangiocarcinoma) to allow for the most accurate delineation of tumors for
treatment planning.
3. Treatment Planning:
Various patient characteristics must be considered when treating liver tumors with proton therapy, including
tumor location, size, and motion; prior treatment history; and baseline liver function. Design of beam
angles and paths require careful consideration of multiple factors that must be individualized for each
patient; no single set of beam arrangements are applicable for all patients. For example, angles that are
optimal for beam robustness may compromise target dose conformality or increase dose to other OARs
and vice versa. Generally, for patients with liver dysfunction, priority is given to selecting beam angles
that are both robust and optimally spare normal liver tissue.
I. Abdomen—Retroperitoneum
1. Rationale:
The median size of retroperitoneal sarcomas is 15 cm at diagnosis, making these among the largest tumors.
Although the primary treatment of these tumors is surgery, local recurrence rate at five years has been
reported to be as high as 50% even from experienced major referral centers. Often times, preoperative
radiation therapy can improve local tumor control when the tumor itself displaces much normal tissue or
perhaps the posterior tumor margin is difficult to resect. A randomized phase III study conducted by the
European Organization for Research and Treatment of Cancer European Organization for Research and
Treatment of Cancer (EORTC) (the STRASS study) that randomized patients with retroperitoneal sarcomas
to either surgery alone or preoperative radiation therapy was a negative trial with preoperative radiotherapy
at 50.4 Gy RBE generating a small effect on abdominal recurrence-free survival (RFS). However, a post
hoc subgroup analysis suggested that preoperative radiotherapy might improve outcomes for patients with
liposarcoma and low-grade retroperitoneal sarcoma, which comprised 75% of the subjects. In patients with
liposarcomas, the abdominal RFS significantly favored preoperative radiotherapy over surgery alone [99].
Preoperative dose escalation to the high-risk posterior tumor margin, which is often very close or
positive, has been associated with improved local tumor control. Protons are being evaluated in an
ongoing clinical trial testing the safety and efficacy of further dose escalation to this margin, with
separate scanned proton and photon IMRT cohorts to determine whether protons permit higher dose,
less toxicity, or both, or alternatively whether proton therapy permits the use of an ultrahypofractionated
approach with less toxicity and improved patient convenience and cost-effectiveness.
2. Immobilization and Simulation:
CT simulation is performed in the supine position with the patient’s arms positioned comfortably above
their head and preferably with knee/ankle rests for leg support [71]. An immobilization device may be
used (eg, vacuum fix bag). No specific bladder or bowel preparation is required except when the sarcoma
is primarily located within the pelvis. In that situation, the degree of rectal and bladder filling should be
assessed and documented at simulation with efforts to reproduce this during radiation. Oral and IV
contrast may be used to aid in the delineation of targets and organs at risk if required, but a useful
alternative is to co-register diagnostic MR or CT imaging with the simulation data set. The extent of the
planning CT simulation scan is dependent on the overall size and position of the target but may need to
PRACTICE PARAMETER 13 Radiation Oncology Proton Therapy
extend above the diaphragm (eg, tracheal bifurcation) and caudally to the level of the lesser trochanter. For
smaller targets in the pelvis, the upper abdomen may be excluded, and, for upper abdominal targets, the
pelvis may be excluded. Generally, the maximum slice thickness should be no more than 2 to 3 mm. The
use of 4-D CT scans and respiratory gating apparatus are dependent on the position and motion of the
target. For upper abdominal targets, the use of these to minimize or account for target motion is highly
desirable, whereas, for lower abdominal or pelvic targets, respiration has a less significant effect on target
motion and thus the use of these techniques may be omitted. Planning target volume (PTV) margins will
range from 0.5 to 1.0 cm depending on image guidance.
3. Treatment Planning:
To help with gross tumor volume (GTV) delineation, registration of the diagnostic CT or T1-weighted
postgadolinium MR scan with the free-breathing planning CT may be performed. However, this is not
always necessary, because the GTV is often readily visible on the planning CT scan. The GTV should
be contoured on the 4-D CT scan (to incorporate motion) and labeled internal GTV (iGTV). An
international sarcoma expert radiation oncology consensus group developed guidelines for the clinical
target volume (CTV) and internal target volume (ITV) delineation [100]. The ITV is the sum of the iGTV
and CTV, the latter of which is defined as a 1.5-cm symmetric expansion of the iGTV. The ITV is then
edited at interfaces of bone, retroperitoneal compartment, liver, and kidneys and cropped 3–5 mm below
the skin surface. It is further edited such that the ITV expands 5 mm into bowel and air cavities; if the
tumor extends to the inguinal canal, a 3-cm inferior expansion is added to the iGTV (as per extremity soft-
tissue sarcoma.) The ITV should extend fully into retroperitoneal and abdominal wall musculature. If the
ipsilateral kidney is planned to be resected, it is not necessary to edit the ITV to exclude this kidney. The
recommended PTV is a 5-mm expansion to the ITV if frequent image guidance will be obtained; if this
is not the case, a larger PTV expansion should be used. The recommended preoperative dose is 50–50.4
Gy in 1.8–2 Gy fractions. In addition to treating the entire retroperitoneal tumor to moderate dose (45–
50 Gy), there has been interest in the concept first described by Tzeng et al of preoperative dose
escalation to the part of the tumor considered to be at risk for positive margins following surgery. This
is typically the region of tumor abutting the posterior abdominal wall, vertebral bodies, and great
vessels; consensus guidelines have delineated the appropriate approach [101]. Early reports for this
technique delivering 57 Gy in 25 fractions to the high-risk margin were encouraging, but further data for
both safety and efficacy are warranted before this approach should be considered standard practice [102].
A Massachusetts General Hospital–led multicenter Phase I-II trial of proton and photon dose escalation is
in progress. Until such data are available, preoperative dose escalation is best delivered only on protocol
[103].
The selection of treatment beams should minimize the effect of bowel gas on the dosimetry. Often,
combinations of PA, posterior oblique, and lateral beams are appropriate. Evolving proton arc techniques
weighted posteriorly may also show benefit. Cone beam CT or replanning CT scans should be considered
during treatment to validate the PTVs and allow for adaptive planning if any significant changes in the
tumor occur over the course of treatment [104].
J. Pelvis—Genitourinary, Rectum, Anal, Gynecologic
1. Rationale:
The absence of exit dose with protons may permit improved sparing of bowel, rectum, bladder,
uterus/ovaries or testes, and hip joints when irradiating tumors in the pelvis. This may be important in
reducing acute and late toxicity of radiation therapy. Fertility preservation without ovarian pexation may
be achieved in some patients with protons depending on the relationship of the target volumes to the ovaries.
Other unique scenarios in which proton therapy may confer an advantage over photon therapy in the pelvis
include patients with multiple synchronous pelvic malignancies requiring radiation; patients with
inflammatory bowel diseases or other bowel disease that place them at increased risk of side effects and/or
malignancy with radiation therapy; or patients with a single kidney or transplanted pelvic kidney with
treatment of an adjacent target volume and in whom maximal avoidance of the transplanted organ is critical.
2. Immobilization and Simulation:
Patients are generally treated supine, often in simple cushioned knee-foot lock, vacuum-lock, or other
PRACTICE PARAMETER 14 Radiation Oncology Proton Therapy
similar immobilizing device with arms elevated. Some patients with posterior pelvic tumors, such as
sarcomas arising in the sacrum, may benefit f r o m prone positioning that may facilitate treatment with
PA proton fields. A strategy for ensuring reproducibility with a constant amount of bladder filling, either
by emptying the bladder or treating with a full or defined bladder volume (ie, instructing patient to empty
bladder and drink 12 ounces of fluid 15 minutes before treatment), is advised and can be adjusted based
on patient needs determined at simulation. Similarly, an endorectal balloon may be employed in certain
scenarios to ensure some consistency ad reproducibility of the rectum while immobilizing the clinical target
volume (eg, prostate or prostate bed) [38,105,106].
3. Treatment Planning:
If oral or IV contrast is employed, the planners may need to manually correct the attenuation to water
density for treatment planning. Treatment gantry angles should be chosen to minimize the impact of
variable bowel and bladder filling. Concurrent MRI simulation is often used for genitourinary and
gynecologic subsites to improve soft tissue delineation.
4. Special considerations:
a. Pelvic nodes
Protons with pencil beam scanning allow treatment of pelvic and para-aortic lymph nodes with a
reduced dose to the bowel; this may have particular benefit for patients with increased radiation
sensitivity, such as with inflammatory bowel disease. Beam angles should be chosen that minimize the
possible effects of bowel gas and variable bladder distention on the intended dose distribution and thus
may be favored posteriorly and laterally if needed [107,108]. Special attention should be given to proton
penumbra for deep-seated tumors when penumbra could be as high as 15 mm [3].
b. Prostate Cancer
A randomized clinical trial and a large, multi-institutional, nonrandomized pragmatic trial of protons
versus IMRT for treatment of prostate cancer have both recently completed accrual, with results
pending [109]. Recent studies have similarly established the feasibility and efficacy in treating the
prostatic fossa in the adjuvant setting [106,110,111] and is the subject of a randomized trial of proton
versus photon therapy including hypofractionated regimens [112]. A clinical advantage for protons is
related to the reduction in rectal, urinary, and erectile dysfunction toxicity [20] as measured through
Common Terminology Criteria for Adverse Events (CTCAE) graded toxicity and/or patient reported
outcomes, as well as a reduction in the risk of secondary malignancies [112,113]. Whether any RBE
differences result in improved biochemical and local control as suggested by a recent National Cancer
Database (NCDB) analysis [114] is the subject of secondary endpoints in the aforementioned clinical
trials. As with treatment with IMRT, fiducial markers help with target localization, and rectal balloons
or rectal spacers (used in appropriate indications) [115] may help limit the dose to the rectum.
c. Gynecologic Cancers
The dosimetric benefit of proton therapy in gynecologic cancers has been explored [116] in the setting
of adjuvant therapy for posthysterectomy patients [117], extended pelvic field irradiation for
endometrial cancer [118], cervical cancer [119], and recurrent vaginal cancer [120]. Protons may allow
for delivery of high radiation doses to patients with pelvic sidewall and/ or local recurrences of
gynecologic cancers, particularly in the reirradiation setting. An ongoing prospective phase II trial is
examining the ability of adaptive proton therapy to reduce the impact on morbidity and the immune
system in cervical cancer [121]. If protons are used for these or for locally advanced gynecologic
malignancies, similar considerations as with prostate cancer with regard to bowel gas and bladder
distention are important [117] in mitigating intra- and interfraction variability and dose delivery
uncertainties.
d. Sarcoma and Desmoid Tumors
Protons have a long history of use for sarcomas and soft-tissue tumors in permitting dose escalation
and retreatment of areas such as the pelvis that are difficult to manage with surgery and/or in medically
inoperable patients [122-125]. Protons allow delivery of high radiation doses to pelvic sarcomas that
are unresected or resected with positive margins, in which the necessary doses for tumor control exceed
bowel and other OAR tolerances [126]. T4 colonic tumors may be adherent to the pelvic side wall,
PRACTICE PARAMETER 15 Radiation Oncology Proton Therapy
where protons may permit delivery of dose escalated radiation to these areas with improved sparing of
pelvic viscera.
e. Rectal Cancer or Colonic “T4”
Proton therapy can be used for initial irradiation or reirradiation of the pelvis in patients with
locally recurrent rectal cancer, which often involves the pelvic sidewall or presacral tissues and
in which radiation dose escalation, often in conjunction with chemotherapy, may be important for local
disease control. These patients often require maximal sparing of surrounding OARs (bowel, bladder,
ureters, pelvic bone, pelvic nerves) from additional radiation because of previously delivered
radiation or prior or upcoming surgical interventions. Proton therapy used in initial treatment of
rectal cancers preoperatively is currently under investigation. Special circumstances such as active
inflammatory bowel disease or young age may warrant consideration of proton therapy in these patients
[127-129]. Relatedly, T4 colonic tumors may be adherent to the pelvic side wall, where protons may
permit delivery of dose escalated radiation to these areas with improved sparing of pelvic viscera [130].
f. Anal Cancer
Protons appear to reduce normal tissue radiation dose in the chemoradiation treatment of anal cancer,
which often requires irradiation of a large target volume encompassing the primary site as well as
perirectal, pelvic, and inguinal nodes. Protons may reduce the risk of acute and late radiation treatment-
associated morbidity [131,132].
Definitive treatment of anal cancers with chemoradiation is frequently associated with severe skin,
GI, genitourinary, and hematologic toxicities, largely owing to the irradiation of large target volumes
encompassing the primary site as well as perirectal, pelvic, and inguinal nodes. Proton therapy may
reduce radiation dose to small bowel, bladder, genitalia, and pelvic bone marrow with the potential to
reduce the risk of acute and late radiation treatment-associated morbidity. The ability to achieve
superior skin sparing in the inguinal and perianal regions compared to photons is uncertain and will
depend on the specific planning technique being applied.
g. Fertility
Protons have provided the opportunity for both ovarian and testicular sparing from exit radiation dose
with the need for ovarian pexation or secondary testicular shielding. This can be critical in young
patients for maintaining fertility [133,134].
h. Testicular cancer (Seminoma)
Radiation therapy has evolved to play a limited but important role in the management of early-stage
testicular seminoma (stage I and II). Because the clinical target generally involves the para-aortic nodes
in patients with a relatively young median age, they may benefit from the reduction in integral dose and
sparing of adjacent OARs [135-137]. Proton beam therapy for testicular seminoma resulted in excellent
clinical outcomes and was associated with lower rates of acute diarrhea compared to photon therapy
[138].
K. Pediatrics
Many of the principles surrounding adult disease sites apply to pediatric patients with cancer. For other aspects of
proton therapy in children, these principles serve as a starting point that should be further modified to
accommodate considerations of physical and mental development.
1. Anesthesia
Anesthesia is commonly required for the immobilization of young children [139]. As with photon therapy,
this is an individualized decision that incorporates a child’s stage of development, the physical
discomfort of positioning, and the necessary radiation technique. For children undergoing proton
therapy, three elements require additional consideration. First, proton therapy delivery may require a longer
treatment session and therefore an extended period of immobilization. Second, the precision of proton
therapy means it is very unforgiving to even slight movement associated with a young child’s anxiety
or agitation. Third, an average proton therapy gantry and/or treatment vault is often much larger in size
PRACTICE PARAMETER 16 Radiation Oncology Proton Therapy
and scale compared to modern linear accelerators. This often translates into a more intimidating
environment for young children. To address these unique considerations, centers may find a certified child
life specialist valuable for patient preparation and subsequent delivery of proton therapy [140]. The use
of virtual reality techniques to reduce or eliminate the need for daily sedation is being explored at multiple
centers [141].
2. Growth Effects
Although valuable in the avoidance of critical organs, the sharp dosimetric gradient of proton therapy may
create asymmetry in developing bones and soft tissue, causing suboptimal functional or cosmetic outcomes
[142]. Although this has been considered in some photon settings (such as Wilms tumor), the potential
impact may be greater with proton therapy. In some situations a pediatric radiation oncologist may
intentionally treat a larger volume to minimize the likelihood of developmental asymmetry. However, this
approach is being challenged with current strategies that intentionally spare the anterior vertebral body in
proton craniospinal irradiation (CSI) in children. The potential long-term musculoskeletal impact of vertebral
body sparing CSI is being evaluated in ongoing trials [143].
3. Secondary Tumors
Through the absence of exit dose, proton therapy consistently delivers a lower total body integral radiation
dose compared to photon therapy delivered with the same number of beams. This is especially critical in
children, who have a higher lifetime risk of radiation carcinogenesis. Initial modeling studies using older
proton technology suggested out of field neutron scatter dose may lead an unexpected incidence of
secondary tumors, but this is refuted by clinical outcomes [144]. Furthermore, newer techniques of pencil
beam scanning, which reduces the hardware in the proton beam path, produce a neutron dose
comparable to modern photon delivery. The use of any proton therapy has an approximate half reduction
of integral radiation dose to nontarget tissues compared to photon therapy techniques [113,145].
L. Radiation Sensitivity
1. Reirradiation
Reirradiation requires integration of prior radiation dose delivered in addition to current desired treatment
[146,147]. Prior radiation plans should ideally be reconstructed to determine the extent of potential dose
overlap. Beam arrangements should ideally seek to avoid overlap with the prior dose as much as possible.
Generally, some dose discount can be made from prior irradiation, theoretically with approximately 50%
dose discount for every five years removed from the present time and with more conservative discount when
considering more highly radiation sensitive structures with more dire associated toxicity (eg, optic chiasm,
brainstem). While proton therapy may be the most optimal way to deliver repeat external beam radiation
therapy in many cases [148], with the potential for fewer toxicities relative to photon reirradiation, high-
grade complications are still possible with proton reirradiation [149], especially when the composite and
time decay adjusted dose to the target significantly exceeds the tolerance of involved normal tissues.
2. Medical Comorbidity
Patients with underlying disorders or conditions that increase ionizing radiation sensitivity will still carry
such risks with treatment by proton therapy. It is possible, however, that the use of proton therapy to reduce
or avoid collateral organ irradiation will achieve better tolerance to radiation therapy. For example, proton
therapy of a brain tumor may reduce nontarget brain irradiation and thereby reduce the risk of a multiple
sclerosis flare. Proton therapy to the spine will often avoid all radiation exposure to the GI track and
thereby may prevent an inflammatory bowel disease flare.
3. Combined drug therapies
Some chemotherapeutics known to sensitize radiation (eg, gemcitabine), some novel targeted agents (eg,
vemurafenib), and many checkpoint inhibitors can accentuate combined modality treatment toxicity.
Proton therapy may be helpful to reduce treatment toxicity by reduction of nontarget tissue radiation
exposure. Although the incidence and severe of toxicities may be reduced [150], practitioners should not
assume that the combination of systemic agents with proton therapy will be without risk, and caution
should still be employed when providing proton therapy under high-risk or untested circumstances.
PRACTICE PARAMETER 17 Radiation Oncology Proton Therapy
IV. DOCUMENTATION
Documentation should be in accordance with the ACR–ASTRO Practice Parameter for Communication: Radiation
Oncology and the ACR–AAPM Technical Standard for the Performance of Proton Beam Radiation Therapy [33,40].
V. PROCESS OF THERAPY AND EQUIPMENT SPECIFICATIONS
The ACR–AAPM Technical Standard for the Performance of Proton Beam Radiation Therapy contains specifics
regarding beam delivery and properties, dosimetry, geometry and dose-volume definition, treatment planning,
motion management, imaging for treatment localization, and uncertainties [33]. Here, we present a short summary of
these topics.
The diversity in existing and available technology to produce clinical proton beams necessitates highly specialized
onsite technical knowledge of the delivery system based on vendor-specific training in order to set up appropriate
technical policies and procedures (eg, radiation safety).
To ensure continuous accurate absolute dose calibration, clinics are encouraged to follow the International Atomic
Energy Agency, Absorbed Dose Determination in External Beam Radiotherapy IAEA TRS 398 protocol and to
participate in the Imaging and Radiation Oncology Core (IROC) annual independent dose verification program. In
addition, initial IROC credentialing procedures are mandatory for participation in National Cancer Institute (NCI)-
supported clinical trials.
For volume definition, it is recommended to follow International Commission on Radiation Units and Measurements
(ICRU) reports 62 and 78, with a special emphasis on the consideration of various sources of uncertainty.
Dose computation for proton therapy is highly sensitive to tissue densities, as represented by CT Hounsfield units.
Therefore, proper characterization of each CT scanner’s Hounsfield unit to relative proton stopping power conversion
is essential. In this regard, dual energy CT (DECT) may be advantageous [151]. Any devices used for patient
immobilization must be proton-compatible, ie, minimally disturb the traversing particle beam, and avoid sharp density
gradients. Immobilization and patient support must be considered for dose calculation. Motion management strategies
are of great importance, particularly when treating with scanned particle beams. Clear guidelines for treatment of
moving targets should be developed. When available, Monte Carlo simulation or TPS with Monte Carlo algorithms are
recommended to be employed for dose computation.
Commissioning of the treatment planning system should follow general procedures also used in conventional
therapy (eg, IAEA TRS 430). Furthermore, it is recommended to apply an RBE of 1.1 for the conversion between
physical and biological dose (ICRU 78); however, the RBE may be variable depending on the cell line histology and
fraction size as described in TG-256 [152].
Image guidance for patient setup is required in proton therapy. Various technologies are available with both 2-D and
3-D techniques. These should be validated and checked according to the existing ACR–ASTRO Practice Parameter
for Image-Guided Radiation therapy (IGRT) [34].
During the treatment planning process, the impact of range uncertainties should be assessed. Robustness planning
analysis and assessment may be performed on a site-specific basis, when first establishing a treatment protocol, or
on a patient-specific basis when special concerns arise. Before moving on to treatment, phantom validation must be
performed in each treatment modalities.
The ACR–AAPM Technical Standard for the Performance of Proton Beam Radiation Therapy presents
recommendations regarding all aspects of a proton QA program [33]. This section briefly summarizes its most
important aspects.
It is recommended to develop QA procedures following the formalism suggested by AAPM TG100, which introduces
the concept of Failure Mode and Effect Analysis in Radiotherapy. This approach improves both effectiveness and
efficiency of QA efforts. The AAPM TG224 [153] report contains more prescriptive tests and acceptance criteria
for proton beams that could be used, similar to TG142.
PRACTICE PARAMETER 18 Radiation Oncology Proton Therapy
Some aspects of a proton beam QA program are set up very similarly to standard photon therapy procedures. These
include mechanical QA (AAPM TG142), calibration of dosimetry equipment (IAEA, TRS 398), chart review and
treatment planning system QA (ICRU 78, IAEA, TRS 430).
Dosimetric machine QA is not standardized and requires a specialized set of procedures and equipment because the
physical quantities to be validated differ from conventional therapy. In addition, methods must be adjusted based on
the vendor and beam delivery system; passively scattered and uniformly scanned beams require different types of
tests than spot scanned beams. Proton centers are encouraged to develop a dosimetric QA program based on available
literature, the nature of their equipment, and already gained institutional experience.
Patient specific QA should cover any field specific hardware and dosimetric checks. The latter can take the form
of actual measurement (eg, single point or 2-D planes) or a computed secondary monitor unit (MU) check in the
case of passive scattering and log file analysis combined with Monte Carlo simulations for spot scanned beams.
With the introduction of new technologies, oftentimes guidelines of technical standards and procedures are produced
in-house but proper validation and documentation of each step and implementation should be documented.
Before initiation of a clinical proton radiotherapy program, it is recommended to hold a treatment readiness
review. Periodic external phantom dosimetric verification through IROC is highly encouraged.
VI. QUALITY CONTROL AND IMPROVEMENT, SAFETY, INFECTION CONTROL, AND PATIENT
EDUCATION
Policies and procedures related to quality, patient education, infection control, and safety should be developed and
implemented in accordance with the ACR Policy on Quality Control and Improvement, Safety, Infection Control,
and Patient Education appearing under the heading Position Statement on QC & Improvement, Safety, Infection Control,
and Patient Education on the ACR web site (https://www.acr.org/Advocacy-and-Economics/ACR-Position-
Statements/Quality-Control-and-Improvement).
Specific proton therapy QA procedures require a thorough understanding of the system design under consideration.
As detailed in the ACR–AAPM Technical Standard for the Performance of Proton Beam Radiation Therapy, QA
policies and procedures should be developed according to detailed Failure Mode Effect Analysis (FMEA) principles
[33,154,155]. These should include explicit detail of the FMEA-identified specific mitigations required to achieve a
safe system along with the associated QA procedures and frequencies necessary to test that such specific mitigations
are implemented correctly. These should include QA procedures for mechanical components, beam calibrations,
treatment planning systems, and machine-specific considerations. Patient-specific QA procedures, medical physics
chart review, implementation of new procedures, associated documentation of QA procedures, and peer review,
including both on-site and remote monitoring, should all be addressed.
1. QA and Performance Improvement (QAPI) Program
Periodic review of the quality assessment and performance improvement (QAPI) program for Proton Therapy
should be performed with selected personnel in Proton Therapy (radiation oncologists, Qualified Medical
Physicists, dosimetrists, radiation therapists, nurses, and administrative staff). Participating in an incident reporting
and learning system is necessary to facilitate continuous quality improvement and patient safety.
2. Credentialing and Training
The training requirements of the radiation oncologist should conform to the qualifications and certification as
outlined in the ACR–ASTRO Practice Parameter for Radiation Oncology [32]. Because this training did not
include proton therapy, specific training in proton therapy must be obtained before performing any such
procedures. The American Board of Radiology has approved fellowship training programs in proton therapy
within several academic medical centers across the United States.
PRACTICE PARAMETER 19 Radiation Oncology Proton Therapy
3. Continuing Medical Education
Continuing medical education programs with an emphasis on proton therapy disease management, planning, and
outcomes shall include radiation oncologists, medical physicists, medical dosimetrists, and radiation therapists.
The continuing education of the physician and Qualified Medical Physicist should be in accordance with the ACR
Practice Parameter for Continuing Medical Education [37].
ACKNOWLEDGEMENTS
This practice parameter was developed according to the process described under the heading The Process for
Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-
Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters–
Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ARS.
Writing Committee – members represent their societies in the initial and final revision of this
practice parameter
ACR
ARS
Steven Jay Frank, MD, Chair
Curtiland Deville, M.D
Zhongxing Liao, M.D.
Indra Das, PhD
Zhongxing Liao, M.D.
Brian Davis, MD
Susan L. McGovern, M.D
Rahul Parikh, M.D
Simon Lo, MD
Rahul Parikh, M.D
Michael Reilly, PhD
Charles B. Simone, II, M.D.
Committee on Practice Parameters – Radiation Oncology
(ACR Committee responsible for sponsoring the draft through the process)
Naomi R. Schechter, MD, Chair
Matthew Harkenrider, MD
Brian Davis, MD
Simon Lo, MD
Anupriya Dayal, MD
Bryan Rabatic, MD
Steven Jay Frank, MD
Michael Reilly, PhD
Laura Freedman, MD
Hina Saeed, MD
Adam Garsa, MD
Paul E. Wallner, DO
William Small, Jr, MD, FACR, Chair of the Commission on Radiation Oncology
Comment Reconciliation Committee
Join Y. Luh, MD, Chair
Zhongxing Liao, M.D.
Nolan Kagetsu, MD, Co-Chair
Simon Lo, MD
Timothy Crummy, MD
Susan L. McGovern, M.D
Indra Das, PhD
Rahul Parikh, M.D
Brian Davis, MD
Michael Reilly, PhD
Curtiland Deville, M.D
Naomi R. Schechter, MD
Steven Jay Frank, MD
Charles B. Simone, II, M.D.
Amy Kotsenas, MD
William Small, Jr, MD
Paul Larson, MD
PRACTICE PARAMETER 20 Radiation Oncology Proton Therapy
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104. Wong P, Dickie C, Lee D, et al. Spatial and volumetric changes of retroperitoneal sarcomas during pre-
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105. Both S, Wang KK, Plastaras JP, et al. Real-time study of prostate intrafraction motion during external beam
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106. Deville C, Jr., Jain A, Hwang WT, et al. Initial report of the genitourinary and gastrointestinal toxicity of post-
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107. Butala AA, Ingram WS, O'Reilly SE, et al. Robust treatment planning in whole pelvis pencil beam scanning
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108. Whitaker TJ, Routman DM, Schultz H, et al. IMPT versus VMAT for Pelvic Nodal Irradiation in Prostate
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PRACTICE PARAMETER 25 Radiation Oncology Proton Therapy
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111. Santos PMG, Barsky AR, Hwang WT, et al. Comparative toxicity outcomes of proton-beam therapy versus
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112. Koerber SA, Katayama S, Sander A, et al. Prostate bed irradiation with alternative radio-oncological
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113. Xiang M, Chang DT, Pollom EL. Second cancer risk after primary cancer treatment with three-dimensional
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115. Hamstra DA, Mariados N, Sylvester J, et al. Continued Benefit to Rectal Separation for Prostate Radiation
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2017;97:976-85.
116. Verma V, Simone CB, 2nd, Wahl AO, Beriwal S, Mehta MP. Proton radiotherapy for gynecologic neoplasms.
Acta Oncol 2016;55:1257-65.
117. Lin LL, Kirk M, Scholey J, et al. Initial Report of Pencil Beam Scanning Proton Therapy for Posthysterectomy
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118. Xu MJ, Maity A, Vogel J, et al. Proton Therapy Reduces Normal Tissue Dose in Extended-Field Pelvic
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119. Shang H, Pu Y, Wang W, Dai Z, Jin F. Evaluation of plan quality and robustness of IMPT and helical IMRT
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120. Li YR, Kirk M, Lin L. Proton Therapy for Vaginal Reirradiation. Int J Part Ther 2016;3:320-26.
121. Corbeau A, Nout RA, Mens JWM, et al. PROTECT: Prospective Phase-II-Trial Evaluating Adaptive Proton
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122. Friedman Y, Fildes J, Mizock B, et al. Comparison of percutaneous and surgical tracheostomies. Chest
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123. Kepka L, DeLaney TF, Suit HD, Goldberg SI. Results of radiation therapy for unresected soft-tissue sarcomas.
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124. Seidensaal K, Harrabi SB, Weykamp F, et al. Radiotherapy in the treatment of aggressive fibromatosis:
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125. Guttmann DM, Frick MA, Carmona R, et al. A prospective study of proton reirradiation for recurrent and
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126. Weber DC, Rutz HP, Bolsi A, et al. Spot scanning proton therapy in the curative treatment of adult patients
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127. Abigail T. Berman SB, Tiffany Sharkoski, Katie Goldrath, Zelig Tochner, Smith Apisarnthanarax, James M.
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129. Koroulakis A, Molitoris J, Kaiser A, et al. Reirradiation for Rectal Cancer Using Pencil Beam Scanning Proton
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130. Hawkins AT, Ford MM, Geiger TM, et al. Neoadjuvant radiation for clinical T4 colon cancer: A potential
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131. Mohiuddin JJ, Jethwa KR, Grandhi N, et al. Multi-institutional Comparison of Intensity Modulated Photon
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132. Vaios EJ, Wo JY. Proton beam radiotherapy for anal and rectal cancers. J Gastrointest Oncol 2020;11:176-86.
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134. Lester-Coll NH, Morse CB, Zhai HA, et al. Preserving Fertility in Adolescent Girls and Young Women
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PRACTICE PARAMETER 26 Radiation Oncology Proton Therapy
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137. Simone CB, 2nd, Kramer K, O'Meara WP, et al. Predicted rates of secondary malignancies from proton versus
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138. Pasalic D, Prajapati S, Ludmir EB, et al. Outcomes and Toxicities of Proton and Photon Radiation Therapy for
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139. Owusu-Agyemang P, Popovich SM, Zavala AM, et al. A multi-institutional pilot survey of anesthesia practices
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140. Scott MT, Todd KE, Oakley H, et al. Reducing Anesthesia and Health Care Cost Through Utilization of Child
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154. Huq MS, Fraass BA, Dunscombe PB, et al. Task Group No. 100 method for evaluating QA needs in radiation
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*As of May 2010, all radiation oncology collaborative practice parameters are approved by the ACR Council
Steering Committee and the ACR Board of Chancellors and will not go through the ACR Council (ACR Resolution
PRACTICE PARAMETER 27 Radiation Oncology Proton Therapy
8, 2010). This collaborative radiation oncology practice parameter document becomes effective on the first day of
the first month following 60 days after final adoption by the ACR BOC. This document is scheduled to begin
revision with the other practice parameters and technical standards adopted at ACR Council during the same year.
Development Chronology for this Practice Parameter
20
13 (CSC/BOC)
Amended 2014 (Resolution 39)
Revised 2018 (CSC/BOC)
Revised 2023 (CSC/BOC) - Effective January 1st, 2024
