Understanding the Role of Re-irradiation

Historically, the idea of giving radiation a second time was taboo, but as technologies and data regarding retreatment of an area advanced, radiation oncologists have been able to shape radiation treatments to help patients with recurrent disease with reirradiation. For example, In the 2010s, national trials demonstrated that re-irradiation could be performed safely and effectively for patients with breast cancer. Today, advanced radiation centers offer re-irradiation that can be fine-tuned utilizing new radiation regimens in conjunction with the latest technology and techniques.

Re-irradiation of solid tumors

The feasibility of these approaches depends on many factors, including the type of tumor and location(s) to be treated. For example, patients with head and neck cancers often receive 70 units of radiation for five to seven weeks at initial diagnosis; in the setting of recurrences, reirradiation was studied but often delivered twice daily for several weeks, which is very challenging for patients. However, an ongoing national trial led by Cleveland Clinic radiation oncologist Shlomo Koyfman, MD is evaluating delivery of five treatments of stereotactic body radiotherapy (SBRT) with or without pembrolizumab for patients with recurrent or second primary head and neck cancers.

Similarly, for lung cancer or lung metastases having previously received radiation therapy, Gregory Videtic, MD and Kevin Stephans, MD have used re-irradiation with SBRT (in one to five treatments) to address mediastinal nodes and/or lung lesions. Repeat radiation is also possible to administer intraoperatively in some cases, such as in recurrent colorectal cancers, through research led by Ehsan Balagamwala, MD and Sudha Amarnath, MD.

Emerging imaging diagnostics

Imaging advances such as prostate-specific membrane antigen (PSMA) PET scans have proven helpful for guiding radiation oncologists in determining when limited locoregional recurrences are present and therefore where re-irradiation may be appropriate in prostate cancer. In such cases, prostate cancer experts such as Rahul Tendulkar, MD and Omar Mian, MD can consider SBRT or brachytherapy to treat these recurrences.

“With advanced imaging such as PSMA PET scans, we can perform targeted re-irradiation, which may extend to multiple disease sites in the years to come,” says Cleveland Clinic Director of Breast Radiation Oncology Chirag Shah, MD.

Re-irradiation of breast cancer

This approach is also applicable in challenging areas such as breast tissue. National studies have demonstrated good outcomes with re-irradiation of breast cancer. “This specialized treatment can be done safely in a multidisciplinary setting, working on conjunction with breast surgeons and plastic surgeons,” says Dr. Shah.

This course of treatment may be appropriate for:

• Patients who previously underwent a lumpectomy and radiation and experienced a recurrence in the same breast
• Recurrent breast cancer with lymph node involvement
• Complex recurrences where surgery isn’t an option (Often performed in conjunction with hyperthermia)

“Mastectomy is still the standard of care in patients with local recurrences following previous radiation, but for patients who wish to avoid a mastectomy, this can be an option,” says Dr. Shah.

A national prospective phase 2 trial evaluated repeat lumpectomy and re-irradiation in these cases, and found it was safe and effective with low rates of side effects. However, re-irradiation can be associated with wound complications, and this is one reason having surgical colleagues on the care team is crucial.

For providers looking to refer a patient to a cancer center for re-irradiation, there are many factors to consider, such as the center’s level of expertise and their comfort level performing re-irradiation, their experience determining dose composites as well as the technology available to delivering treatment.

The possibility for re-irradiation will depend on many elements, such as the dose of initial treatment and how long ago it took place. Dr. Shah recommends that providers keep an open mind when considering repeating radiation therapy. “People are often surprised that this is an option, but in many cases it can really help patients.”

Re-irradiation of central nervous system (CNS) tumors

Having treated many patients with progressive CNS tumors such as high-grade gliomas, the Brain Tumor team at Cleveland Clinic’s Taussig Cancer Center has offered numerous strategies for re-irradiation of CNS tumors. “We need to be very thoughtful about approaching re-irradiation, because tissue that has received treatment never fully ‘forgets’, so you want as much recovery time as possible between initial and repeat treatment,” says Erin Murphy, MD.

Currently, the team has three techniques available:

• Pulsed low-dose rate re-irradiation. Depending on the size and location of the tumor and the patient’s performance status, patients with large infiltrating tumors who have received considerable prior treatment may be offered a six-week course of pulsed low-dose rate re-irradiation. A recent trial found that despite receiving nearly twice the initial dose of radiation, patients tolerated this course of therapy well. Progression-free survival was 5.5 months which is often longer than what patients may obtain in the setting of clinical trials for progressed high-grade tumors.
  
  “With this technique, patients receive the same effective dose as their first course of radiotherapy, but the radiation energy is delivered slowly,” explains Dr. Murphy. “This approach is intended to make tumor cells cycle into a more sensitive state where they’re more exposed to treatment. This improves cell kill while giving normal tissues the ability to repair during radiation.” The downside is that this approach doubles the patient’s time on the treatment table to between 30 to 40 minutes.
• Short course of high-dose radiation. Often patients with progressive disease may have fatigue or other symptoms impacting their quality of life. In this context, the radiation oncology team often will prescribe a high-dose treatment given over two weeks. This does not offer the protection of normal tissue that pulsed low-dose re-irradiation does, but for patients with limited treatment options, this can be an appropriate approach to slow tumor growth with less lingering impact on their everyday quality of life. Patients tend to tolerate this treatment well, with similar side effects to initial radiation treatment.
• Focused high-dose radiosurgery. In patients who have a smaller area of recurrence of a primary tumor that is far from critical structures, radiosurgery or Gamma Knife® surgery provides very focused high-dose radiation in one to five sessions. This is typically followed by systemic therapies to control disease progression. “We’ve seen extended durable local control with these techniques,” Dr. Murphy says. “In this case, we can deliver high doses safely for very focal areas of recurrence.”

As with any therapy, there are risks to counsel patients about. “An experienced team that includes radiation and medical oncologists, radiation physicists and radiation therapists familiar with planning and delivering these techniques is critical to minimize risks,” says Dr. Murphy.