Radiation Therapy Updates for Breast Cancer in the NCCN Guidelines

On the second day of the 22nd Annual Conference of the National Comprehensive Cancer Network (NCCN), in Orlando, Florida, Kilian E. Salerno, MD, of the Roswell Park Cancer Institute, walked the audience through updates to the NCCN Guidelines, explaining clinical situations in which radiation is indicated, appropriate targets of radiation treatment, and optimal approaches for minimizing toxicity.

Understanding the target area is important, Salerno said, because the treatment options and the treatment plan and delivery need to be optimized per the patient’s needs. “The target region to receive the radiation dose can vary. It might be the whole breast; partial breast, where we may target the lumpectomy cavity; the chest wall; or just regional nodes.”

The dose varies according to the target region:

1. Conventional fractionation is a dose of 1.8 to 2 Gy per fraction, for a total dose of 45 to 50.4 Gy.

2. Hypofractionation is typically a shorter course that uses larger doses per fraction. More than 2 Gy may be used per fraction to lower the total dose, which can be:

• 40.05 to 42.56 Gy given in daily fractions for whole breast radiation
• 34-38.5 Gy administered as twice daily fractions for partial breast radiation

3. The accelerated course is usually treatment over a shorter time course. Clinics have several options for the source of radiation to choose from, Salerno said. The sources of radiation include:

• External beam (photons, electrons, proton beam)
• Brachytherapy (radioactive source or catheters)
• Intraoperative devices

The NCCN Guidelines for breast cancer, updated in March 2017, provide the guidance on target definition and optimizing therapy for an individual patient as needed. “Greater target dose homogeneity and sparing of normal tissues can be accomplished using compensators such as wedges, forward planning using segments, and intensity-modulated radiation therapy,” the guidelines stated.

The most commonly used techniques include:

• Positioning: supine versus prone. Salerno said that the prone position is used to identify hotspots and minimize damage to normal tissue. It is most typically used for early-stage disease when the whole breast is the target, and it ensures the normal tissue is not affected.
• Computed tomography for based planning
• Three dimensionally planned conformal radiotherapy versus immune-modulated radiation therapy
• Respiratory gating, where the patient controls respiration. This technique requires extra time, personnel, more planning, and time for treatment, Salerno said.

The updated guidelines also provide information on patients who have undergone breast conservation but in whom radiation therapy is contraindicated.

An absolute “No” includes:

• Pregnancy
• Diffuse suspicious or malignant-appearing microcalcifications
• Diffusely positive pathologic margins
• Homozygous for ATM mutations

Relative contraindication in case of:

• Prior radiation therapy to the chest wall or breast
• Active connective tissue disease that involves the skin
• Tumors larger than 5 cm
• Positive pathologic margins
• Women with a suspected predisposition to breast cancer

“Identifying an appropriate margin has been a topic of debate and the new Guideline provides direction,” said Salerno. “We must remember, though, that context matters.” The following 2 recommendations have been added to the Guideline:

• 2 mm is considered an adequate margin in ductal carcinoma in situ treated with whole-breast irradiation.
• For stage 1-II invasive disease treated with whole-breast irradiation, no tumor on ink is considered an adequate margin

Salerno then spoke about locoregional treatment of clinical stage I, IIA, or IIIB disease or node-positive disease. For negative axillary nodes the following treatment options have been recommended:

• Radiation therapy to the whole breast, with or without boost to the tumor bed; preferably hypofractionation
• Accelerated partial breast irradiation in some low-risk patients, following guidelines defined by the American Society of Radiation Oncology, which, Salerno said, will be updated in the coming year.

She then provided insight on post mastectomy radiation (PMRT), classic indications for which include 4 or more positive axillary lymph nodes, positive margins, and tumor size over 5 cm. However, patients with 1 to 3 lymph nodes, close margins and some high-risk features, such as age, extracapsular extension, and certain intrinsic subtypes, could also be considered for PMRT.

Regional node irradiation or RNI is recommended for those with 4 or more positive nodes, strongly considered for 1 to 3 positive nodes, and may be considered for some high-risk node negative patients.