Intraoperative Radiation Therapy

Title XVIII of the Social Security Act, §1862(a)(1)(A) allows coverage and payment for only those services that are considered to be reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, §1862(a)(1)(D) in the case of clinical care items and services provided with respect to research and experimentation.

CMS Internet-Only Manual, Pub. 100-02, Medicare Benefit Policy Manual, Chapter 15, §90 X-Ray, Radium, and Radioactive Isotope Therapy

CMS Internet-Only Manual, Pub. 100-08, Medicare Program Integrity Manual, Chapter 13, §13.5.1 General Requirements

Definitions and Scope:

This policy addresses intraoperative radiation for the treatment of cancer. Intraoperative radiation for the purposes of this Local Coverage Determination (LCD) is any method of radiation administered to the patient in the operating room (OR), such that the initiation of radiation exposure begins following the surgical exposure of the tumor or tumor bed, and the cessation of radiation exposure occurs prior to the patient leaving the OR. This includes radiation that is delivered by a beam from a device or placement of a radioactive material in tissues. Therapeutic radiation delivered as defined by this time frame should be coded using the codes in the related billing and coding article. Therapies termed “brachytherapy” in the medical literature that involve removal of the radiation source prior to the patient leaving the OR should be considered “intraoperative radiation” rather than “brachytherapy” for the purposes of this LCD.

This policy does not address general diagnosis or management of malignancies, nor does it address specific surgical or chemotherapy treatments. Radiation delivered outside of the OR and brachytherapy are not specifically covered here either.

Background:

For many cancers, surgical resection is an established method to either achieve a prolongation of life or a cure. Radiation delivered in conjunction with surgery improves outcomes for some types of cancer presumably through its ability to reduce tumor volume, kill grossly visible neoplastic tissue that was not resected due to technical infeasibility, and destroy microscopic foci of cancer surrounding the known tumor site. However, radiation is toxic not only to the neoplastic but also to healthy tissues, and in some cases mortality benefits due to cancer related deaths appear to be attenuated by non-cancer related mortality from complications of radiation to healthy tissue. Intraoperative radiation has been posed as a radiation delivery method that allows providers to deliver a large dose of radiation focally to the tumor bed, thereby aggressively treating the tumor but sparing healthy tissues.

General Indications and Principles

• Surgical resection of the tumor must be reasonable and necessary for the treatment of the patient’s malignancy based on all available information at the time that the decision to put the patient through surgery is made. As such, the medical record should reflect that surgical resection was indicated. Palmetto GBA recognizes that intraoperative findings may change the course of treatment, and resection may not be carried out or completed in such cases.

• Surgery strictly for the sake of delivery of intraoperative radiation is not supported by the evidence and is not considered reasonable and necessary.

• This LCD is not intended to provide recommendations regarding treatment. Radiation treatment should be reasonable and necessary for a patient’s individual case, in light of that patient’s cancer diagnosis and cancer stage or grade, as well as the patient’s comorbid clinical conditions.

• The choice of radiation dose and areas to irradiate should be derived from evidence-based treatment protocols. The relevant evidence should be on hand for review if requested.

• Radiation treatment planning and delivery should be handled by an experienced and qualified team with the necessary knowledge and skills to ensure that appropriate precautions are taken to protect the patient, healthcare providers, and the public from the hazards of radiation in the OR environment. The relevant professionals with such skills and knowledge who are involved in the case must be documented. All federal, state, and local laws governing the use and handling of radiation must be followed.

General Procedure Requirements:

• Pre-procedural documentation must include a complete initial evaluation, including history and an appropriately focused physical examination with review of relevant pathology and imaging results. Treatment plans formulated in conjunction with other providers (e.g., medical oncologist, surgeon, tumor board, etc.) should be included if these discussions support that the procedure is reasonable and necessary.

• A procedure note must be legible and include sufficient detail to allow reconstruction of the procedure. Required elements of the note include a description of the mode of radiation delivered, anatomic sites to which it is delivered, dose of radiation (in Gray), as well as any necessary pre- and post-procedural assessments. This note must have a legible signature, time, and date.

Information pertaining to specific malignancies based on anatomic location and tissue type

Breast Cancer

Intraoperative Radiation Therapy (IORT) in breast cancer should be used only in patients in whom there is a reasonable expectation at the time of surgery that Accelerated Partial Breast Irradiation (APBI) may be appropriate. Even in patients who meet these criteria, clinicians should provide appropriate informed consent regarding the fact that whole breast irradiation is still considered standard treatment. Palmetto GBA considers patients to be appropriate for APBI based on the criteria set forth by the National Comprehensive Cancer Network (NCCN) to describe candidacy for use of APBI outside of a clinical trial. These criteria are as follows:

1. A woman who meets all of the following criteria:

• 50 years or older

• Invasive ductal carcinoma

• Tumor size <= 2cm (T1 disease)

• Negative margins >= 2mm

• No lymphovascular invasion

• Estrogen receptor (ER) positive

• BRCA negative

or

2. A woman who meets all of the following criteria:

• Low or intermediate nuclear grade

• Screen-detected ductal carcinoma in situ (DCIS)

• Tumor size <= 2.5 cm

• Negative margins >= 3 mm

Palmetto GBA recognizes that new findings following surgery, including but not limited to final pathology results, may be found, and that based on such findings the patient would be determined not to be a suitable candidate based on the above criteria after the IORT dose has already been given. As long as information is available at the time of surgery that indicates it is reasonable to expect that the patient did meet the above criteria, IORT may still be considered reasonable and necessary. If further radiation treatment is deemed necessary based on the new information learned after IORT is given, further radiation should be provided as clinically appropriate.

Intraoperative radiation is not considered reasonable and necessary in women who undergo a complete or a radical mastectomy.

Colon and Rectal Cancer

Intraoperative radiation for colon cancer may be reasonable and necessary in patients who warrant surgical resection and at least 1 of the following:

• T4 tumor

• Recurrent cancer

• Positive or close surgical margins

Intraoperative radiation may be given as a boost dose in conjunction with pre- or post-operative external beam radiation.

Soft Tissue Sarcoma

Intraoperative radiation may be considered reasonable and necessary in the treatment of soft tissue sarcomas for which there is a substantial risk that surgical resection will be insufficient to avoid local recurrence because of the tumor’s location, surrounding anatomy, or other technical aspects of the procedure which may limit surgical effectiveness. 

Uterine and Cervical Cancer

Intraoperative radiation may be considered reasonable and necessary in patients with recurrent tumor burden following external beam radiation. Intraoperative radiation may also be considered reasonable and necessary in patients without metastatic disease for whom surgical resection by itself would be unlikely to achieve adequate local disease control.

Gastric and Gastroesophageal Junction Cancer

Intraoperative radiation is not currently considered reasonable and necessary in the treatment of gastric and gastroesophageal junction cancers.

Pancreatic Cancer

Intraoperative radiation is not currently considered reasonable and necessary in the treatment of pancreatic cancer.

Esophageal Cancer

Intraoperative radiation is not currently considered reasonable and necessary in the treatment of esophageal cancer.

Lung Cancer

Intraoperative radiation is not currently considered reasonable and necessary in the treatment of lung cancer.

Brain Cancer

Intraoperative radiation is not currently considered reasonable and necessary in the treatment of brain cancer.

Breast Cancer

For many women with breast cancer, surgical resection is an important component of treatment. This resection may involve either mastectomy or breast-conserving therapy (BCT) depending on the tumor histology and disease stage. For some women, breast conserving surgery in conjunction with radiation may offer similar cancer-related outcomes as mastectomy.^1-5 The standard of treatment has conventionally been post-operative external beam whole breast radiation delivered over roughly 3 weeks. However, APBI has started to gain interest as a possible therapeutic approach that may increase accessibility of adequate radiation treatment and BCT to women.⁶ Intraoperative radiation in breast cancer is among potential APBI delivery methods.

Initial research has provided some evidence that IORT may be non-inferior to and equivalent to whole breast irradiation in women who have had BCT with regards to tumor recurrence, potentially offering reduced radiation toxicity.^7-9 However, whole breast irradiation is still considered the standard treatment option per NCCN guidelines.

NCCN guidelines generally consider APBI including IORT experimental and recommend its use in clinical trials. But note that it may be appropriate for women who meet specific criteria.¹⁰ These criteria are as follows:

1. A woman who meets all of the following criteria:

• 50 years or older

• Invasive ductal carcinoma

• Tumor size <= 2cm (T1 disease)

• Negative margins >= 2mm

• No lymphovascular invasion

• ER positive

• BRCA negative

or

2. A woman who meets all of the following criteria:

• Low or intermediate nuclear grade

• Screen-detected DCIS

• Tumor size <= 2.5 cm

• Negative margins >= 3 mm

Colorectal Cancer

For decades, a treatment for colorectal cancer has been surgical resection. However, recurrence rates post-operatively and mortality are quite high, particularly among rectal carcinomas.¹¹ The use of pre-operative and post-operative adjuvant therapies has been tried to improve outcomes. A large study of externally applied radiation in rectal cancer found that while external beam radiation enhanced outcomes related to the primary cancer, an overall mortality benefit, while present, was attenuated by a rise in the rate of non-rectal cancer related deaths among radiation treated patients. This suggested that benefits of radiation could be improved if the safety of radiation could be enhanced.¹²  

Intraoperative radiation has been developed as a potential method of delivering a high dose of radiation to a focused area of concern for malignancy, while limiting radiation exposure and toxicity to non-cancer tissue.

There are no large randomized controlled trials (RCTs) of intraoperative radiation in colorectal cancer, and 2 smaller RCTs showed local tumor control, but no 5 year mortality benefit of intraoperative radiation in populations with a large proportion of T3 cancers.^13-14 However, a number of non-randomized comparative and non-comparative studies have collectively indicated that IORT provides both enhanced local tumor control and a mortality benefit, particularly in patients with T4 tumors and not unresectable or positive margin tumors.¹⁵

NCCN guidelines for the treatment of colon and rectal cancers recommend consideration of intraoperative radiation in patients who have at least 1 of the following characteristics of their cancer^16-17:

• T4 tumor

• Recurrent cancer

• Positive or close surgical margins

Soft Tissue Sarcoma

Soft tissue sarcoma is relatively rare, but treatment is difficult. Surgical resection is a mainstay of treatment.¹⁸ However, for retroperitoneal sarcomas, which can be quite large and involve numerous anatomic areas, complete resection is often not achievable, and even with complete resection, recurrence rates are still quite high.¹⁹ This prompted interest in the use of radiation, which must be applied to a large area near many organs that are potentially quite sensitive to radiation.

This prompted an interest in intraoperative radiation in the treatment of soft tissue sarcomas. There is limited evidence on the use of intraoperative radiation with only a single RCT studying its effect in retroperitoneal sarcomas, which showed a significant reduction in local disease recurrence at 5 years.²⁰ A number of observational studies have also suggested that intraoperative radiation may have a benefit in the treatment of retroperitoneal sarcomas.²¹

Uterine and Cervical Cancer

The management of uterine and cervical cancer has variation among oncologists, though surgical resection is often an important component in the treatment of endometrial cancer. While no large RCTs exist, smaller studies and observational studies suggest that intraoperative radiation may be an appropriate means of delivering a sufficiently large dose of radiation to involved tissues while sparing healthy tissues of the pelvis in appropriately selected patients with uterine cancer and may be an appropriate treatment option in patients with recurrent cervical cancer.^22-24

NCCN guidelines recommend that intraoperative radiation be considered in patients with recurrent tumor burden following external beam radiation or in patients for whom surgical resection by itself would be unlikely to achieve adequate local disease control.^25-26

Gastric and gastroesophageal junction cancers

Surgical resection has been a mainstay of treatment for gastric cancer. External beam radiation, when combined with chemotherapy, has been shown to improve survival.^27-28 Due to concerns for toxicity, intraoperative radiation has been an area of interest, but data from recent RCTs and trials comparing intraoperative radiation to external beam radiation are lacking. Observational and single-arm studies have not consistently shown that intraoperative radiation provides a clear benefit in relation to well proven treatment options.²⁹

Guidelines from NCCN recommend the use of external beam radiation where radiation is appropriate.^30-31

Esophageal cancers

Surgical resection has been a mainstay of treatment for esophageal cancer. External beam radiation in conjunction with chemotherapy has been shown to improve survival and has become an important component of surgically treated esophageal cancers.^32-35 However, there is a paucity of high quality research examining the benefits of intraoperative radiation.

Pancreatic Cancer

Most pancreatic cancers are unresectable, and among those that are, the prognosis for 5 year survival is still quite poor. Radiation has been pursued as a way to enhance survival, including IORT. NCCN guidelines explicitly indicate that there is no known role for IORT in pancreatic cancer.³⁶

There have been observational studies employing IORT, but there have been no large RCTs, and the evidence that has been published does not suggest a mortality benefit.^29,37 NCCN guidelines note that there is no clearly identified role for intraoperative radiation in the treatment of pancreatic cancer.

Lung Cancer

Surgical treatment is an important component of many patients with non-small cell lung cancer.^38-41 However, there is a lack of evidence regarding the use of intraoperative radiation.

Surgical treatment is generally not considered indicated in small cell lung cancer, which would preclude the use of intraoperative radiation. In the subpopulation of patients with small cell lung cancer for whom limited evidence suggests surgery may offer appropriate treatment, there is a paucity of evidence regarding the use of intraoperative radiation.^42-43

Intraoperative radiation is not considered reasonable and necessary in the treatment of lung cancer.

Brain

While whole brain radiation has become a recognized component of high grade gliomas, studies using intraoperative radiation have been limited to small observational studies, with inconsistent results.^44-45 While there is a phase I/II trial currently underway, intraoperative radiation for brain cancer is presently an experimental treatment and not reasonable and necessary.⁴⁶

Intraoperative radiation has been studied in a variety of conditions and has been shown to offer specific benefits over alternative radiation delivery methods for some conditions.

In the treatment of breast cancer, evidence supports the use of a single dose of IORT in lieu of a course of external beam radiation to the whole breast in selected women who undergo breast-sparing surgery, producing similar disease recurrence outcomes as whole breast irradiation with potentially less toxicity to healthy tissues and may be an appropriate treatment approach for appropriately selected women.

In colon and rectal cancers, evidence supports the role of intraoperative radiation for reducing local disease recurrence and potentially prolonging life in colon and rectal cancers for which there is significant concern that surgical resection will be incomplete.

Soft tissue sarcomas can be difficult to treat in their entirety surgically, leaving small amounts of malignant tissue, and they may be close to radiation-sensitive tissues. There is evidence that intraoperative radiation may reduce local disease recurrence in these tumors.

For recurrent uterine and cervical cancers, in which there is a role for surgery, and in cancers for which there is a reason to be concerned about surgical resection not getting all malignant tissue, evidence suggests that IORT may have a treatment benefit.

For gastric and esophageal cancers, evidence supports a benefit of treatment regimens using combined external beam radiation and chemotherapy. These findings in conjunction with a lack of data supporting the use of intraoperative radiation, mean that intraoperative radiation is not currently reasonable and necessary in the treatment of gastric cancer and esophageal cancer.

There is a paucity of evidence regarding the use of IORT in the treatment of pancreatic cancer, lung cancer, and brain cancer. At this time, intraoperative radiation for these diagnoses is not considered reasonable and necessary.

Documentation Requirements

Documentation supporting medical necessity should be legible, maintained in the patient’s medical record and made available to the A/B MAC upon request. 

Any diagnosis submitted must have documentation in the patient’s record to support coverage and medical necessity.

1. Fisher B, Anderson S. Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233-1241.
2. Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast-preserving surgery in women with localized cancer of the breast. N Engl J Med. 1993;328(22):1587-1591.
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5. Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513-520.
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