Clinical Policy: Proton and Neutron Beam Therapies

Reference Number: CP.MP.70
Date of Last Revision: 11/24
Coding Implications
Revision Log

See Important Reminder at the end of this policy for important regulatory and legal
information.

Description

Proton beam therapy (PBT) is a form of external beam radiation therapy (EBRT) that utilizes
protons (positively charged subatomic particles) to precisely target a specific tissue mass. Proton
beams can penetrate deep into tissues to reach tumors, while delivering less radiation to
surrounding tissues. This may make PBT more effective for inoperable tumors, or for those areas
in which damage to healthy tissue would pose an unacceptable risk.

Neutron beam therapy (NBT) is a less widely available form of EBRT that utilizes neutrons. Its
clinical use is very limited due to difficulties in the delivery of this treatment modality.

Policy/Criteria

I. It is the policy of health plans affiliated with Centene Corporation® that proton beam therapy
(PBT) is medically necessary for the following indications:
A. Ocular tumors, including but not limited to, intraocular melanomas;
B. Primary spine or spinal cord tumors or metastatic tumors of the spine or spinal cord for
which organ-at-risk tolerance may be exceeded with photon treatments;
C. Tumors that approach or are located at the base of the skull, including but not limited to,
chordoma or chondrosarcoma;
D. Hepatocellular cancer and intra-hepatic biliary cancers;
E. Primary or benign solid tumors or other hematologic malignancies in members/enrollees
≤ 21 years old;
F. Tumors/cancers that can be treated with any other type of radiation in members/enrollees
with a known genetic mutation/syndrome increasing the risk of cancer;
G. Malignant and benign primary CNS tumors, excluding IDH wild-type glioblastoma
(GBM);
H. Pituitary neoplasms;
I. Advanced staged and unresectable head and neck cancers;
J. Cancers of the nasopharynx, nasal cavity, paranasal sinuses and other accessory sinuses,
when normal tissue constraints cannot be met by photon-based therapy;
K. Non-metastatic retroperitoneal sarcomas;
L. Re-irradiation cases where cumulative critical structure dose would exceed tolerance
dose;
M. Primary tumors of the mediastinum, including thymic tumors (i.e. thymoma, thymic
carcinoma, mediastinal tumors and mediastinal lymphomas (i.e. Hodgkin lymphoma and
Non-Hodgkin lymphoma), and thoracic sarcomas;
N. Non-small cell lung cancer, to spare critical structures when critical organ dose
constraints cannot be met with photon therapy (including three dimensional and IMRT
neutron techniques);
O. Malignant pleural mesothelioma;
P. Primary malignant or benign bone tumors;

Q. Medically inoperable patients with a diagnosis of cancer typically treated with surgery
where dose escalation is required due to the inability to receive surgery;
R. Primary and metastatic tumors requiring craniospinal irradiation;
S. Primary cancers of the esophagus;
T. Advanced and unresectable pelvic tumors with significant pelvic and/or peri-aortic nodal
disease;
U. Members/enrollees with a single kidney or transplanted pelvic kidney with treatment of
an adjacent target volume and in whom maximal avoidance of the organ is critical.
V. Salivary gland tumors.

II. It is the policy of health plans affiliated with Centene Corporation that neutron beam therapy
(NBT) is medically necessary in the treatment of salivary gland tumors when meeting any of
the following:
A. The tumor is considered surgically unresectable, recurrent, or is resected with gross
residual disease or positive margins;
B. Member/enrollee is medically inoperable.

III.It is the policy of health plans affiliated with Centene Corporation that all other indications
for PBT and NBT are considered not medically necessary as insufficient evidence exists to
recommend proton and/or neutron beam therapy as superior to other treatments available.

Background

Proton beam therapy (PBT) is an important method of treatment used in managing malignant
disease with a well-defined target. Unlike x-rays, protons cause little damage to the tissues they
pass through to reach their destination. Their energy is released after traveling a specified
distance, thus delivering more radiation to the tumor and doing less damage to the nearby normal
tissue. Because of this, PBT may be more useful for tumors with distinct edges rather than those
whose edges are mixed with normal tissue.

Radiation therapy (RT) plays a critical role in the local tumor control of benign and low-grade
central nervous system tumors in children but is not without the risk of long-term treatment-
related sequelae. PBT is an advanced RT modality with a unique dose-deposition pattern that
allows for treatment of a target volume with reduced scatter dose delivered to normal tissues
compared with conventional photon RT and is now increasingly utilized in children with the
hope of mitigating radiation-induced late effects.¹

The American Society of Radiation Oncology (ASTRO) evaluated the evidence of use of PBT
and listed examples of indications for coverage of PBT in their 2023 Model Policy for PBT,
which includes, but is not limited to the following:

1. The target volume is near one or more critical structures and a steep dose gradient
   outside the target must be achieved to avoid exceeding the tolerance dose to the critical
   structure(s), which would portend a higher risk of toxicity.

2. A proton-based technique would decrease the probability of clinically meaningful
   normal tissue toxicity by lowering an integral dose-based metric and/or organ at risk dose
   volume constraint associated with toxicity.

3. The same or an immediately adjacent area has been previously irradiated, and the dose
   distribution within the patient must be sculpted to avoid exceeding the cumulative
   tolerance dose of nearby normal tissue.²(p.3)

ASTRO states there is a need for continued clinical evidence development and comparative
effectiveness analyses for the appropriate use of PBT for various disease sites and as such all
other indications are suitable for Coverage with Evidence Development (CED). They note that
radiation therapy for patients treated under the CED paradigm should be covered by the
insurance carrier as long as the patient is enrolled either in an IRB-approved clinical trial or in a
multi-institutional patient registry adhering to Medicare requirements for CED.²

Head and Neck Cancer

Guidelines from National Comprehensive Cancer Network (NCCN) regarding PBT in the
treatment of head and neck cancer state the following. “Achieving highly conformal dose
distributions is especially important for patients whose primary tumors are pericural in location
and/or invade the orbit, skull base, and/or cavernous sinus; extend intracranially or exhibit
extensive perineural invasion; and who are being treated with curative intent and/or who have
long life expectancies following treatment. Non-randomized single institution clinical reports
and systematic comparisons demonstrate safety and efficacy of PBT in the above-mentioned
specific clinical scenarios. Proton therapy can be considered when normal tissue constraints
cannot be met by photon-based therapies, or when photon-based therapy causes compromise of
standard radiation dosing to tumor or postoperative volumes.”³(p.2)

Central Nervous System Cancers

NCCN guidelines note that it is reasonable to consider proton beam therapy for craniospinal
irradiation where available, as it is associated with less toxicity.⁴

Uveal Melanoma

Per NCCN guidelines on uveal melanoma, “Tumor localization for proton beam therapy may be
performed using indirect ophthalmoscopy, transillumination, and/or ultrasound (intraoperative or
postoperative but before proton beam), x-ray, MRI and/or CT.”⁵(p.2)

A practice parameter on PBT from the American College of Radiology/ASTRO also notes that
“commonly, the ophthalmologist will guide patient selection with tumor/target definition through
techniques such as funduscopy 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. 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. Other
alternative approaches have been devised when special eye line is not available.”⁶

Non-metastatic Retroperitoneal Sarcomas

Per NCCN guidelines on soft tissue sarcoma (STS), surgical resection of a localized tumor with
negative margins is the standard, potentially curative treatment for patients with
retroperitoneal/intra-abdominal STS. Radiation therapy (RT) can be administered as preoperative
treatment for patients with resectable disease or as a primary treatment for those with

unresectable disease. Post-operative RT is discouraged but may be considered in rare instances.
Newer RT techniques such as IMRT and 3D conformal RT using protons or photons may allow
tumor target coverage and acceptable clinical outcomes within normal tissue dose constraints to
adjacent organs or risk. When EBRT is used, sophisticated treatment planning with IMRT,
tomotherapy and/or proton therapy can be used to improve therapeutic effect. However, the
safety and efficacy of adjuvant RT techniques have yet to be evaluated in a multicenter RCT.
RT is not a substitute to definitive surgical resection with negative margins, and re-resection to
negative margins is preferable.⁷

Hepatocellular Cancer

Per NCCN guidelines on hepatocellular carcinoma (HCC), EBRT is a treatment option for
patients with unresectable disease, or for those who are medically inoperable due to comorbidity.
All tumors irrespective of the location may be amenable to RT [3D conformal RT, IMRT, and
stereotactic Body Radiation therapy (SBRT)]. Image-guided radiotherapy is strongly
recommended when using EBRT, IMRT, and SBRT to improve treatment accuracy and reduce
treatment-related toxicity. Hypofractionation with photons or protons is an acceptable option for
intrahepatic tumors, though fractionation at centers with experience is recommended. PBT may be
appropriate in specific situations.⁸ In a phase II study, 94.8% of patients with unresectable HCC
who received high dose hypofractionated PBT demonstrated >80% local control after two years,
as defined by RECIST criteria.⁹ Several ongoing studies are continuing to investigate the impact
of hypofractionated PBT on HCC outcomes, including randomized trials comparing PBT to
radiofrequency ablation (RFA). Data has demonstrated that local control is exceptional
regardless of the fractionation used.¹⁰ In a phase III study using the Child-Pugh classification, an
evaluation of clinical outcomes of PBT versus RFA demonstrated PBT could be applied safely in
patients with small recurrent hepatocellular carcinoma. The two-year local progression-free
survival (LPFS) rate was 94.8% versus 83.2% respectively, demonstrating that PBT is not
inferior to RFA treatment.¹¹

Prostate Cancer

ASTRO recommends coverage of PBT for the treatment of non-metastatic prostate cancer when
enrolled in an institutional review board (IRB)–approved study or a multi-institutional registry
that adheres to Medicare requirements for Coverage with Evidence Development (CED).²
NCCN guidelines note that there lacks clear evidence to support a benefit or decrement to proton
therapy over IMRT for either treatment efficacy or long-term toxicity. Firm conclusions
regarding differences in toxicity or effectiveness of proton and photon therapy cannot be drawn
because of the limitations of the available studies.¹²

Thymomas and Thymic Carcinomas

Per NCCN, PBT has been shown to improve dosimetry compared to IMRT allowing better
sparing of the normal organs (lungs, heart, and esophagus). Additionally, favorable results in
terms of both local control and toxicity have been obtained with PBT. Based on these data, PBT
is considered an appropriate treatment option.¹³

Hodgkin Lymphoma

Per NCCN, “Treatment with photons, electrons or protons may all be appropriate, depending on
clinical circumstances. Advanced RT technologies such as intensity-modulated RT

(IMRT)/volumetric modulated arc therapy (VMAT), deep-inspiratory breath hold (DIBH) or
respiratory gating, image-guided RT (IGRT), and proton therapy may offer significant and
clinically relevant advantages in specific instances to spare important normal OARs and decrease
the risk for late, normal tissue damage while still achieving the primary goal of local tumor
control.”¹⁴(p.1)

Esophageal and Esophagogastric Junction Cancers

NCCN guidelines indicate this emerging technique may offer protection of normal tissue by
limiting exposure of adjacent organs to radiation in addition to lowering the rates of post-
operative pulmonary, cardiac, gastrointestinal, and wound complications. The guidelines
recommend that patients with esophageal cancer be treated with PBT within a clinical trial,
noting that data is early and evolving.¹⁵ An overall low-quality body of evidence suggests that
PBT has possible benefit for the treatment of esophageal adenocarcinoma (EAC). PBT may have
similar effectiveness to both IMRT and 3DCRT and results in significantly reduced radiation
exposure to adjacent organs at risk. PBT could possibly result in fewer complications than IMRT
(intensity-modulated radiation therapy) and 3DCRT (3-dimensional conformal radiation therapy)
among patients undergoing esophagectomy, however the statistical significance of these findings
was mixed. The rate of nonoperative complications was comparable between PBT and IMRT.¹⁶
According to ASTRO’s 2023 Model Policy for PBT, published clinical data supports the use of
PBT for primary cancers of the esophagus.²

Neutron Beam Therapy (NBT)

NBT utilizes neutrons, rather than photons, to destroy tumor cells. Neutrons are much heavier
than photons and appear to be more effective at causing damage to very dense tumors. It is
however more clinically difficult to generate neutron particles, so it has not gained wide
acceptance for treatment. It has most commonly been studied in salivary gland tumors which are
either unable to be removed completely or for recurrent disease.

NCCN states NBT was historically considered a promising solution for unresectable salivary
gland cancer, however, they no longer recommend NBT as a general solution for salivary gland
cancers due to the diminishing demand, high rates of long-term toxicity over time, concerns
regarding the methodologic robustness of available randomized trial data, and closure of all but
one center in the U.S. The panel recognizes the potential clinical value of neutron therapy for
select patients.³

Coding Implications

This clinical policy references Current Procedural Terminology (CPT®. CPT® is a registered
trademark of the American Medical Association. All CPT codes and descriptions are copyrighted
2023 American Medical Association. All rights reserved. CPT codes and CPT descriptions are
from the current manuals and those included herein are not intended to be all-inclusive and are
included for informational purposes only. Codes referenced in this clinical policy are for
informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage.
Providers should reference the most up-to-date sources of professional coding guidance prior to
the submission of claims for reimbursement of covered services.

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CLINICAL POLICY
Proton and Neutron Beam Therapies

https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf. Published May 14, 2024. Accessed October 16, 2024.