1. health and fitness
2. disease
3. cancer

Clinical Policy Title: Proton Beam Therapy
Clinical Policy Number: 05.02.01
Effective Date:
Initial Review Date:
Most Recent Review Date:
Next Review Date:
December 1, 2013
August 21, 2013
Sept. 18, 2013
August, 2014
Policy contains:
• Proton therapy;
• Particle or hadron therapy;
• Cancer;
• Brain AVM.
Lines of Business: AmeriHealth Caritas VIP Plans clinical policies are subject to all applicable
laws and government regulatory requirements of the geographical areas served. Refer to the
pertinent government and plan documents for each geographical area for guidance. Individual
member benefits must be verified.
Policy Definition:
AmeriHealth Caritas VIP Plans covers health care service/items when they are medically
necessary and not prohibited from coverage by state or federal laws and/or regulatory
requirements. This AmeriHealth Caritas VIP Plans clinical policy addresses the medical evidence
supporting the use of proton therapy.
AmeriHealth Caritas VIP Plans considers the use of Proton Beam Therapy to be clinically proven
as the effectiveness of its use has been established in peer reviewed professional literature.
These clinical policies, along with other sources, such as plan benefits and state and federal
laws and regulatory requirements, including any State or plan specific definition of medically
necessary, are considered by AmeriHealth Caritas VIP Plans when making coverage
determinations.
Coverage Policy:
AmeriHealth Caritas VIP Plans considers the use of Proton Beam Therapy to be clinically proven;
and therefore, a finding of medical necessity is supported when the following criteria are met:
•
Solid tumors with documentation of rationale for consideration of Proton Beam Therapy
rather than conventional treatments.
•
Be In one of the following categories:
o in children up to age 18: primary and variant forms of medulloblastoma;
astrocytoma; glioblastoma--OR
o benign or malignant tumors of the base of the skull or axial skeleton –OR—
1
o Benign or malignant primary and secondary tumors of the brain and spinal
cord—OR-o acoustic neuroma craniopharyngioma –OR-o Pituitary and pineal gland tumors;--OR-o intraocular melanoma;
o Metastases to the brain for which standard radiation therapy is not appropriate;
o Soft tissue sarcoma for which standard radiation therapy is not appropriate.
AND
•
Patient-specific documentation (with imaging studies and details for any previous
treatments) providing the rationale for proton therapy as the treatment of choice versus
conventional approaches may be provided,
AND
•
Research protocol participation: IRB-approved studies requiring informed consent.
A finding of medical necessity is not supported for all other uses of Proton Beam Therapy
Limitations:
• Hematogenous malignancies, e.g., leukemias and lymphomas, are not eligible.
• Case-by-case decisions for metastases with documentation as for primary lesions as above.
Alternative Covered Services: Standard surgical therapies, radiation therapies and
chemotherapies as appropriate for the clinical condition.
Intensity modulated radiation (IMRT) and three-dimensional conformal radiation (3DCR), both
covered in Table 1 reviews and the glossaries (pages 5-7) are now the standards for
conventional radiotherapy in cancer.
Background:
Proton beam therapy: a form of radiotherapy which uses beams of charged sub-atomic
particles in contrast to the photon beams of conventional radiation (X-rays). Proton beams
have potential benefits for the treatment of tumors in cases where surgical excision is deemed
impossible or unacceptably risky.
The first published use of proton beam therapy was in 1954, however the extremely high cost
of producing charged particles inhibited its widespread use. Trikalinos (AHRQ; 2009) reports
seven US centers for proton therapy and an additional four under construction, at costs per
center of $100 to $225 million.
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Proton therapy is classified among particle or hadron therapies, which have different
properties than X-rays. Theoretical advantages of particle beams include more precise delivery
of higher doses to tumor targets and less exposure to surrounding tissues: in other words,
more effective cancer treatment with fewer adverse effects. Due to the large investment for
building a proton therapy facility, treatment costs are higher than with conventional radiation.
It is therefore important to evaluate whether the medical benefits of proton therapy are large
enough to balance the higher costs.
Proton beam therapy is not suitable to all tumor types but may be of particular benefit treating
superficial lesions (such as those of the eye), intermediate depth lesions (such as the head and
neck), and for tumors where conventional radiotherapy would damage surrounding tissue to an
unacceptable level (optical nerve, spinal cord, central nervous system, head, neck, and
prostate). In addition, proton beam may be ideal for use in pediatric patients. This policy
focuses on adult cancers or brain arteriovenous malformations.
Study types consulted in preparing this policy: Systematic reviews pool results (quantitatively
in a meta-analysis or qualitatively) from multiple studies to achieve larger sample sizes and
greater precision of effect estimation than in smaller primary studies. Systematic reviews use
pre-determined transparent methods to minimize bias: effectively treating the review as a
scientific endeavor, thus are rated highest in evidence grading hierarchies.
Economic analyses (cost-effectiveness, -benefit or -utility studies, which report both costs and
outcomes; but not simple cost studies), sometimes referred to as efficiency studies, also rank
near the top of evidence hierarchies. Economic analyses may be attempted and even published
during developmental stages of new healthcare technologies/interventions, but are generally
premature before definitive information on effectiveness is available. Table 1 presents
systematic reviews and economic analyses published (as of August 2013) for proton therapy
and Table 2 other coverage policies.
Table 1: Systematic reviews/guidelines and economic analyses for proton beam therapy:
reverse chronological order and then alphabetically by first author
Citation
Content
Cancer reviews
Hayes Inc. (2013)
Ramaekers (2010)
Proton beam for prostate cancer:
• abstracts provide conflicting evidence;
• Full text review not conducted for this publication and pending
status not noted.
• No CMS coverage decisions identified.
Radiotherapy (IMRT, carbon ion, or proton) in head and neck cancers:
• 1990-2010: English-language clinical studies with ≥10 subjects;
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Citation
Content
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Cancers: naso-pharyngeal; oro-pharyngeal; para-nasal; sino-nasal;
mucosal melanoma; adeno-cystic carcinoma;
Ns with each stage, radiation dose, mean/median age, and
proportion receiving chemotherapy varied among studies;
Reporting of adverse effects varied;
86 observational studies; 8 comparative; Ns, 10-323.
Inclusion of small observational studies and overall heterogeneity
of studies may have adversely effected reliability.
Main results:
• Carbon ions associated with longer survival for mucosal melanoma
Vs protons;
• Tumor control and survival similar for IMRT and protons except for
para- and sino-nasal.
• Carbon-ions and protons associated with lower toxicity rates than
IMRT.
Bauman (Cancer
Intensity modulated radiation therapy in prostate cancer:
Care Ontario; 2010) • 2000- Mar, 2009;
• Systematic reviews, clinical practice guidelines, health technology
assessments, randomized Phase II or III trials;
• ≥50 patients reported in English;
• IMRT recommended over 3DCRT for localized prostate cancer
where dose escalation (>70 Gy) is required;
• Insufficient evidence for post-operative use.
Flynn (2010)
Are there cancer diagnoses for which rigorous research has shown
proton therapy to be effective?
• Systematic reviews, guidelines, or technology assessments:
searches updated to April 2010 for subsequently-published and
review eligible studies to confirm or refute conclusions of published
reviews;
• 12 reviews on a variety of cancers: lung; base of skull; ocular;
prostate; head and neck; and on brain AVMs;
• Reviews concur: most published studies are observational;
• Only prostate cancer and uveal melanoma represented by CCTs
with serious methods weaknesses;
• Economic evaluations premature;
• Overall: insufficient evidence for effectiveness.
Grutters (2010)
Radiotherapy with photons, protons and carbon ions for non-small
cell lung cancer:
• 1994-Aug 2008;
• Studies with ≥ 20 patients published in English or Dutch and
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Citation
Content
reporting two- or five-year survival by stage and adverse events;
• 30 studies (n = 2611); five for proton (180); all case series without
controls;
• Survival with particle therapy higher than conventional radiation
for stage I inoperable; may reduce adverse events in Stage III.
• Further RCT evidence needed.
Grutters (2010a)
CEA: particle therapy in non-small cell lung cancer:
• Decision analytic Markov model to synthesize “all available
evidence” (Grutters, 2010; row above) for inoperable Stage I NSCLC
• Inoperable stage I: carbon-ion cost €67.257/QALY gained
compared to SRS;
• Considerable uncertainty to results: more evidence is needed.
Trikalinos (AHRQ;
Particle beam radiation therapies for cancer:
• Medline, -July 2009:
2009)
• any study design;
• > 10 subjects and describing outcomes or adverse events;
• English; German; French; Italian; Japanese.
• 243 eligible studies; proton alone or in combination with other
interventions for common (prostate) or uncommon cancers (skull
base or uveal melanoma);
• N, 10-2645; median 63;
• FU, 5-157 months; median 36.
• 9 non-randomized comparisons reported in 13 papers with 4086
unique patients;
• Overall: no study found particle therapy significantly better than
alternatives for patient-relevant outcomes.
Subsequently published cancer review (section above) eligible
Yu (2013)
Cross-sectional:
• All Medicare patients with prostate cancer receiving proton or
IMRT, 2008-9;
• Multivariate logistic regression to identify factors associated with
receipt of proton;
• 27,647 men: 2% received proton, 98% IMRT;
• Proton patients: younger, healthier, from more affluent areas than
IMRT;
• Median reimbursement: proton, $32,428; IMRT, $18,575;
• Proton associated with significantly lower genitor-urinary toxicity at
six months: 5.9% Vs 9.5% (OR, 0.60; CI, 0.38-0.96); no difference at
12 months.
• NS differences in GI or other toxicity at 6 or 12 months.
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Citation
Content
Brain AVMs
Van Beijnum (2011) Brain AVMs:
• 2000- March 2011;
• Consecutive case series with≥ 15 patients of any age receiving
microsurgery, stereotactic radio-surgery, or embolization;
• English; French; German; Italian; or Spanish language and
reporting: length of FU; rates of post-op hemorrhage and death;
Ross (Cochrane;
2010)
Main results:
• 137 studies with 142 cohorts (13,698 subjects with 46,314 patientyears FU);
• No RCTs published or included;
• Case fatality:
o Microsurgery, 1.1(CI, 0.87-1.3)/100 patient-years FU;
o Stereotactic radio-surgery, 0.50 (CI, 1.5-1.8);
o Embolization, 1.7 (1.3-2.3);
• Complications leading to permanent neurologic deficits or death:
o Microsurgery, median 7.4% (range 0-40);
o SRS, 5.1% (0-21);
o Embolization, 6.5% (0-28);
• AVM obliteration:
o Microsurgery, 96% (0-100);
o SRS, 38% (0-75)
o Embolization, 13% (0-94);
• Insufficient evidence and too much variation among studies for
valid conclusions.
Interventions for brain AVMs in adults:
• 1980-Nov 2009;
• RCTs comparing interventions against each other or with usual
medical management and reporting relevant clinical outcomes (
partial obliteration or total eradication);
One ongoing/unpublished RCT (ARUBA; enrolling patients with AVMs
that never bled) meets selection criteria; two others (one published;
one not) tested embolic procedures against each other but did not
report outcomes required for this review.
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Table 2: Other guidelines/coverage
Citation
Content
CMS L29263 (2011)
Proton beam radiotherapy: In general, not indicated for widely
disseminated cancers (hematogenous primary or metastases as in
leukemia) or as a short-term palliative procedure.
Group 1 conditions:
• Benign or malignant conditions otherwise not suitable for IMRT or
3DCR: base of skull or axial skeleton but not limited to chordoma
or chohdroscararcoma;
• Solid tumors in children up to age 16: primary and variant forms of
medulloblastoma; astrocytoma; glioblastoma; AVMs; acoustic
neuroma craniopharyngioma; benign and atypicalmeningiomas;
pineal gland tumors; intraocular melanoma;
• Many radiological oncologists believe proton an option where IMRT
or 3DCR is medically necessary, so this contractor will consider it
reasonable for Group #2 ICD-9-CM codes when criteria below are
met (1, 2, or 3) AND (5 or 6; with 6 mandatory):
1. Dose constraints to normal tissues limit total dose safely
deliverable to tumor by other means.
2. Reason to believe that doses thought to be above those
attainable by by other means may improve tumor control.
3. Higher precision associated with proton beam is clinically
relevant.
4. Primary tumors: Curative intent.
5. Metastatic lesions: expectation of long-term (≥ 2 years) benefit
unobtainable with conventional therapy; and expectation of
complete eradication of the lesion otherwise not obtainable.
6. Mandatory: the patient record documents why proton is
considered treatment of choice for this individual.
Additional provisions: As above AND
• Patient treated in a protocol designed for evidence development or
future publication that is expected to support an outcome
advantage for Medicare patients.
• Protocol per se not sufficient in absence of Institutional Review
Board (IRB) oversight and informed consent.
Group 2 conditions:
• Malignant lesions of head and neck with curative intent;
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Citation
Content
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CMS L31617 (2012)
Malignant lesions of para-nasal and other accessory sinus;
Malignant lesions of prostate;
Advanced stage non-metastatic bladder cancer;
Advanced pelvic tumors including cervix;
Left breast tumors;
Pancreatic and adrenal tumors;
Skin cancer with perineural/cranial nerve invasion;
Unresectable retroperitoneal and extremity sarcoma;
Lung and upper abdominal/peridiaphragmatic cancer;
Malignant lesions of liver, biliary tract, anal canal, rectum.
Lesions not specified are not covered.
Group 1:
• Unresectable benign or malignant CNS including but not limited to
primary and variant: astrocytoma; gioblastoma; meduloblastoma;
acoustic neuroma; craniopharyngioma; meningioma; pineal gland
tumors; AVMs;
• Intraocular melanoma;
• Pituitary tumors;
• Chordomas and chondrosarcomas;
• Advanced stage unresectable tumors of the head and neck;
• Malignant lesions of paranasal sinus and other accessory sinus;
• Unresectable retroperitoneal sarcoma;
• Solid tumors in children;
Group 1 conditions also require documentation:
• Dose Volume Histogram demonstrating one or more critical
structures to be protected by proton beam;
• Dose to control tumor undeliverable within tolerance of normal
tissues;
• Documented clinical rationale: doses and precision “generally
thought otherwise unattainable might improve tumor control.”
• Curative intent for primary lesions.
• Metastatic lesions: expectation of ≥2 year life expectancy not
obtainable by other means.
• Treatment of choice for this individual.
• Patient treated in a protocol designed for evidence development or
future publication that is expected to support an outcome
advantage for Medicare patients.
• Protocol per se not sufficient in absence of Institutional Review
Board (IRB) oversight and informed consent.
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Citation
Content
Group 2 conditions:
• Unresectable lung and upper abdominal/peridiaphragmatic
cancers.
• Unresectable pelvic tumors including with periaortic nodes and
cervix.
• Unresectable pancreatic and adrenal tumors.
• Skin cancer with macroscopicperineural/cranial nerve or base of
skull invasion.
• Unresectable cancer of: liver; biliary tract; anal canal; rectum.
• Localized, non-metastatic prostate cancer although no good
comparative data with external beam, IMRT, or brachytherapy.
• T and N staging by CT or MRI;
• Dose to control tumor undeliverable within tolerance of normal
tissues;
• Documented clinical rationale: doses and precision “generally
thought otherwise unattainable might improve tumor control.”
• Curative intent for primary lesions.
• Metastatic lesions: expectation of ≥2 year life expectancy not
obtainable by other means.
• Treatment of choice for this individual.
• Patient treated in a protocol designed for evidence development or
future publication that is expected to support an outcome
advantage for Medicare patients.
• Protocol per se not sufficient in absence of Institutional Review
Board (IRB) oversight and informed consent.
Glossary of terms:
Arteriovenous malformation (AVM): an abnormal connection between arterial and venous
systems that can occur anywhere in the body but is most dangerous in the brain. While many
AVMs cause no symptoms and are discovered only at autopsy, those in the brain can be
associated with headaches, epilepsy, hemorrhagic stroke, or death. They are treated by
embolization (cutting off the blood supply with a coil, balloon, particle, or glue via catheter),
neurosurgery, or radiation. A Cochrane review (Ross, 2010) found no randomized trials to
confirm the superiority of any AVM treatment over alternatives.
Searches for this policy (August 2013) confirmed that no more recent publications change that
conclusion. The single ongoing review-eligible trial [A Randomized Trial of Unruptured Brain
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AVMs (ARUBA)] cited by the Cochrane reviewers still not published as of August 10, 2013.
ARUBA began in October 2006 and is investigating invasive interventions (endovascular
procedures, neurosurgery, or radiotherapy; alone or in combination) versus medical
management. The ARUBA protocol available at www.clinicaltrials.gov does not explicitly
include proton therapy in the list of invasive procedures.
Carcinoma: A malignant and invasive tumor of epithelial (skin or other body surface) cells that
spreads by metastasis and can recur after surgery.
Chordoma: an uncommon and relatively slow-growing tumor of the brain or brain stem and
arising from remnants of an embryonic structure, the notochord, which otherwise disappears
during fetal life.
Cochrane Collaboration: an international effort by 31,000 clinicians, researchers, and staff,
most of whom contribute their time to conducting and updating the highest quality systematic
reviews to support informed health care decision making. The collaboration also maintains a
large collection of clinical trial records. Reviews and trial records are published as the Cochrane
Library.
The Collaboration is named for Archie Cochrane (1909-88), a Scottish physician and early
proponent for adopting the scientific method (randomized controlled trials) in clinical research.
3-dimensional conformal therapy (3DCRT): computed tomography-based techniques to
deliver radiation more accurately and with higher doses. These techniques include the use of
conformal particle beams, intensity-modulated photon (X-ray) beams, and proton beams.
Conformal photon-beam therapy has become the standard external radiation therapy, although
the more technically challenging intensity-modulated radiation is becoming more widely used.
Decision analysis: The methods and procedures for formalizing decision making: analyzing
options, consequences and uncertainties by probabilities; and often representing the process
graphically by a tree, algorithm, or other diagram. In health care policy formulation, metaanalysis (in systematic reviews) decision analysis, and economic evaluation are related methods
to quantitatively synthesize information in order to arrive at a summary conclusion, e.g., on
efficacy or effectiveness, and to resolve uncertainty about resource allocation (Petitti, 1994).
Efficacy Vs. effectiveness: Efficacy is impact on clinical outcomes in a research setting;
effectiveness, impact in the less controlled “real world” setting of widespread clinical use.
Randomized controlled trials (RCTs) demonstrate the former but are designed to optimize
internal validity rather than generalizeablity to other settings.
Gray (Gy): unit of absorbed radiation dose.
10
Hemangioma: a benign tumor of tiny blood vessels (capillaries). They may be present at birth
or appear during the first six months. They may occur anywhere in the body, on the skin as
“strawberry birth mark” and on structures near the eye may cause vision problems. Many
hemangiomas regress spontaneously; for those requiring treatment: steroids , propanolol, or
lasers are used with variable effectiveness and adverse effect profiles.
Intensity-modulated radiation therapy (IMRT): along with conformal therapy (defined
below), radiation oncology techniques developed in the 1990s to capitalize on computers’
abilities to plan radiation delivery more precisely, thus maximizing exposure of tumors while
avoiding surrounding tissues.
Macular degeneration: a major cause of visual impairment and blindness in older adults, agerelated macular degeneration (ARMD) damages the macula (central area) of the retina and
causes central visual field vision loss. ARMD can make it difficult to read or recognize faces,
although enough peripheral vision may remain for other activities of daily life.
Markov decision process: a mathematical model used in decision analysis
Non- small-cell lung cancer (NSCLC): referring to microscopic characteristics. Any type of lung
cancer other than small cell, including squamous cell, large cell and adenocarcinoma. Lung
cancer in never smokers is almost universally NSCLC, the majority adenocarcinoma, versus
squamous cell or small cell, which are associated with tobacco use. NSCLCs are relatively
insensitive to chemotherapy and are treated by surgery.
Sarcoma: a malignant tumor arising from tissues originating as embryonic mesenchyme or
mesoderm: bone; cartilage; fat; muscle; vascular; or blood. They are named for the tissues
they most closely resemble microscopically and behave with various levels of aggressiveness.
Stereotactic radiosurgery (SRS): a form of radiation treatment that uses a three-dimensional
external coordinate system to locate small lesions within the body for intervention. It requires a
reliable and stable frame of reference, e.g., bone landmarks with a constant spatial relationship
to soft tissues. Hence SRS applications have generally been restricted to the brain although
stereotactic breast biopsy is also performed. Ross (Cochrane; 2010) classifies proton therapy
among SRS procedures but found no completed RCTs for any brain AVM interventions meeting
eligibility criteria for review.
3-dimensional conformal therapy (3DCRT): computed tomography-based techniques to
deliver radiation more accurately and with higher doses. These techniques include the use of
conformal particle beams, intensity-modulated photon (X-ray) beams, and proton beams.
Conformal photon-beam therapy has become the standard external radiation therapy, although
the more technically challenging intensity-modulated radiation is becoming more widely used.
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Particle therapies: external beam radiation with charged subatomic particles such as protons,
neutrons, or carbon ions (also known as hadrons), as opposed to X-rays, which use photons
(light waves).
Performance status: a measure of cancer patients’ general well-being and ability to perform
activities of daily living; used in clinical practice and research to estimate: ability to tolerate
treatment; appropriate treatment dose; or intensity of palliation.
A frequently used adult performance status scale, the Karnofsky score (KPS) runs from 100
(perfect health) to zero (death):
Karnofsky score
(%)
100
90
80
70
60
50
40
30
20
10
Description
Normal: no complaints, no sign of disease
Normal activity levels; few symptoms or signs of disease
Normal activity with some difficulty, some signs or symptoms
Caring for self but not capable of normal activity or work
Requires some help but can take care of most personal
requirements
Frequent need for help and medical care
Disabled: requires special help and care
Severely disabled: hospital admission indicated but no risk of
death
Very ill: requires urgent admission with supportive measures or
treatment
Moribund: rapidly progressive fatal disease
Quality-adjusted life year (QALY): an outcome measure used in economic analyses; it
incorporates both quantity and quality of life gained through treatment.
Uveal tract: a collective term for internal structures of the eye: iris; ciliary body; and choroid.
Uveal melanoma is a malignant tumor arising from pigmented cells (melanocytes) that produce
eye color.
Related Policies: AmeriHealth Caritas VIP Plans Utilization Management Program Description
REFERENCES
Professional Society Guidelines
Adelaide Health Technology Assessment (AHTA). Proton beam therapy for the treatment of
cancer. Australian Government Department of Health and Aging. June 2006.
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Australia and New Zealand Horizon Scanning Network (ANZHSN). Proton beam therapy for the
treatment of neoplasms involving (or adjacent to) cranial structures. Royal Australasian College
of Surgeons. May 2007.
Australia and New Zealand Horizon Scanning Network (ANZHSN). Proton beam therapy for the
treatment of uveal melanoma. Royal Australasian College of Surgeons. May 2007b
CMS local coverage determination L29263. Proton beam radiotherapy. Wisconsin Physicians
Service Insurance Corporation(Contractor 0952). Illinois. Oversight Region V. Effective
3/17/2012.
CMS local coverage determination L31617. Proton beam radiotherapy. First Coast Service
Options (Contractor 09102). Florida. Oversight Region IV. Effective 2/2/2009; revised
10/1/2011.
Flynn K, Adams E, Alligood E, Curran S, Lawrence V. Proton therapy for cancer. Veterans Health
Administration Office of Patient Care Services. Technology Assessment Program. Boston (MA).
April 2010.
Hayes, Inc. Proton beam therapy for prostate cancer. Search & summary. March 25, 2013.
Jarosek S, Elliott S, Virnig BA. Proton beam radiotherapy in the US Medicare population: growth
in use between 2006 and 2009. Proton Beam Radiotherapy. Data Points #10 (prepared by the
University of Minnesota DEcIDE Center, under Contract No. HHSA290201000131). Rockville,
MD. Agency for Healthcare Research and Quality; May 2012. AHRQ Publication No. 12-EHC005
Moran BJ, DeRose P, Merrick G, Hsu IC, Abdel-Wahab M, Arterbery VE, Ciezki JP, Frank SJ,
Mphler JL, Roswnthal SA, Rosi CJ, Yamada Y. Expert panel on radiation oncology-prostate.ACR
appropriateness criteria®definitive external beam radiation in stage T1 and T2 prostate cancer.
[online publication]. Reston (VA): American College of Radiology (ACR).2007.
Rosenzweig KE, Chang JY, Chetty IJ, Decker RH, Ginsburg ME, Kestin LL, Kong PM, Lally BE,
Langer CJ, Movsas B, Videtic GMM, Willers H, Expert panel on radiation oncology – Lung. ACR
appropriateness criteria®nonsurgical treatment for non-small-cell lung cancer: poor
performance status or palliative intent.[online publication]. Reston (VA): American College of
Radiology (ACR); 2012.
Peer-reviewed
Amichetti M, Cianchetti M, Amelioi D, Enrici RM, Minniti G. Proton therapy in chordoma of the
base of the skull: a systematic review. Neurosurgical Review. 2009; 32:403-16.
Bauman G, Rumble RB, Chen J, Loblaw A, Warde P. IMRT indications expert panel. The role of
IMRT in prostate cancer. Toronto (ON): Cancer Care Ontario (CCO); 2010 Oct 27.
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Bekelman JE, Hahn SM. The body of evidence for advanced technology in radiation oncology
(editorial). Journal of the National Cancer Institute. 2013;105(1):6-7.
Bekkering G, Rutjes AWS, Vlassov VV, Aebersold DM, von Bremen K, Kleijnen J. The
effectiveness and safety of proton radiation therapy for indications of the eye: a systematic
review. Strahlentherapie und Onkologie. 2008;185:211-21.
Van Beijnum J, van der Worp HB, Buis DR, Al-Shahi SR, Kappelle LJ, Rinkel GJ, van der Sprenkel
JW, Vanderop WP, Algra A, Klijn CJ. Treatment of brain arteriovenous malformations: a
systematic review and meta-analysis. Journal of the American Medical
Association.2011;306(18):2011-19.
Brada M, Pijls-Johannesma M, de Ruysscher D. Current clinical evidence for proton therapy.
Cancer Journal .2009; 15(4):319-24.
Efstathiou JA, Gray PJ, Zietman AL. Proton beam therapy and localized prostate cancer: current
status and controversies. British Journal of Cancer. 2013;108:1225-30.
Grutters JP, Kessels AG, Pils JohannesmaM, De Ruysscher D, Joore MA, Lambin P. Comparison
of the effectiveness of radiotherapy with photons, protons and carbon-ions for non-small cell
lung cancer: a meta-analysis. Radiotherapy and Oncology. 2010; 95(1):32-40.
Grutters JP, Pils-Johannesma M, Ruysscher DD, Peeters A, Reimoser S, Severens JL, lambin S,
Joore MA. The cost-effectiveness of particle therapy in non-small cell lung cancer: exploring
decision uncertainty and areas for future research. Cancer Treatment Reviews. 2010a;
36(6):468-76.
Lodge M, Pijls-Johannesma, M, Stirk L, Munro AJ, De Ruysscher D, Jefferson T. A systematic
review of the clinical and cost-effectiveness of hadron therapy in cancer. Radiotherapy and
Oncology.2007;l83(2):110-22.
Lundkvist J, Ekman M, Ericsson SR, Jönsson B, Glimelius B. Proton therapy of cancer: potential
clinical advantages and cost-effectiveness. Acta Oncologica. 2005;44: 850-61.
Olsen DR, Bruland ØS, Frykholm G, Norderhaug IN. Proton therapy: a systematic review of
clinical effectiveness. Radiotherapy and Oncology. 2007;83(2):123-32.
Petitti DB. Meta-Analysis, Decision Analysis, and Cost-Effectiveness Analysis: Methods for
Quantitative Synthesis in Medicine. Monographs in Epidemiology and Biostatistics (#24).
Oxford University Press. New York. 1994.
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Pijls-Johannesma M, Grutters JPC, Verhaegen F, Lambin P, de Ruysscher D. Do we have enough
evidence to implement particle therapy as standard treatment in lung cancer? A systematic
literature review. The Oncologist. 2010.15:93-103.
Ramaekers BL, Pils-Johannesma M, Joore MA, van den Ende P, Langendijk JA, Lambin P, Kessels
AG, Grutters JP. Systematic review and meta-analysis of radiotherapy in various head and neck
cancers: comparing photons, carbon-ions, and protons. Cancer Treatment Reviews.
2011;3793):185-201.
Ross J, Al-Shahi SR.
Interventions for treating brain arteriovenous malformations in adults. Cochrane Database of
Systematic Reviews. 2010, Issue 7.
Trikalinos TA, Terasawa T, Ip S, Raman G, Lau J. Particle beam radiation therapies for cancer.
Technical brief No. 1. (Prepared by the Tufts Medical Center Evidence-based Practice Center
under Contract No. HHSA-290-07-10055.)Rockville, MD: Agency for Healthcare Research and
Quality. Revised November 2009.
Yu JB, Soulos PR, Herrin J, Cramer LD, Potosky AL, Roberts KB, Gross CP. Proton versus
intensity-modulated radiotherapy for prostate cancer: patterns of care and early toxicity.
Journal of the National Cancer Institute. 2013; 105(1):25-32.
Zirtman AL, DeSilvio ML, Slater JD, Rosssi CJ, Miller DW, Adams, JA, Shipley, WU. Comparison of
conventional-dose vs high-dose conformal radiation therapy in clinically localized
adenocarcinoma of the prostate. JAMA. 2005; 294(10) :1233-9.
Moran BJ, DeRose P, Merrick G, Hsu IC, Abdel-Wahab M, Arterbery VE, Ciezki JP, Frank SJ,
Mphler JL, Roswnthal SA, Rosi CJ, Yamada Y. Expert panel on radiation oncology-prostate.ACR
appropriateness criteria®definitive external beam radiation in stage T1 and T2 prostate cancer.
[online publication]. Reston (VA): American College of Radiology (ACR).2007.
Rosenzweig KE, Chang JY, Chetty IJ, Decker RH, Ginsburg ME, Kestin LL, Kong PM, Lally BE,
Langer CJ, Movsas B, Videtic GMM, Willers H, Expert panel on radiation oncology – Lung.ACR
appropriateness criteria®nonsurgical treatment for non-small-cell lung cancer: poor
performance status or palliative intent.[online publication]. Reston (VA): American College of
Radiology (ACR);2012.
Clinical Trials
August 9, 2013: www.clinicaltrials.gov lists 95 in-progress studies for proton beam. One, for
age-related macular degeneration, is randomized.
Centers for Medicare and Medicaid Services (CMS) National Coverage Determination
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The CMS web site (www.cms.gov) lists no national coverage determination documents for
proton therapy.
Local Coverage Determinations: Table 2: CMS 2011 and 2012.
Commonly Submitted Codes:
Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy.
This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding
manuals and bill in accordance with those manuals.
CPT codes
Code
Description
77520
Proton treatment delivery; simple
77523
Proton treatment delivery; intermediate
77525
Proton treatment delivery; complex
Disclaimer: AmeriHealth Caritas VIP Plans has developed clinical policies to assist with making
coverage determinations. AmeriHealth Caritas VIP Plans clinical policies are based on
guidelines from established industry sources such as Centers for Medicare and Medicaid (CMS),
State regulatory agencies, the American Medical Association (AMA), medical specialty
professional societies, and peer reviewed professional literature. These clinical policies, along
with other sources, such as plan benefits and state and federal laws and regulatory
requirements, are considered by AmeriHealth Caritas VIP Plans when making coverage
determinations. AmeriHealth Caritas VIP Plans clinical policies are for informational purposes
only and not intended as medical advice or to direct treatment. Physicians and other health
care providers are solely responsible for the treatment decisions for their patients.
AmeriHealth Caritas VIP Plans clinical policies are reflective of evidence based medicine at the
time of review. As medical science evolves, AmeriHealth Caritas VIP Plans will update its clinical
policies as necessary. AmeriHealth Caritas VIP Plans clinical policies are not guarantees of
payment.
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