Guidelines for Continuing or Holding Systemic Therapy During Radiation Therapy

Continuing or Holding Systemic Therapy During Radiation Therapy

On the Oncology Brothers podcast, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with gastrointestinal (GI) radiation oncologist Nina Sanford, MD, of UT Southwestern, to discuss her guidelines for whether to hold systemic therapy when patients with cancer are undergoing RT.

Dr. Sanford’s framework divides RT into three categories: SBRT, palliative RT, and conventional therapy. The doctors discussed how systemic treatments including cytotoxic chemotherapy, immunotherapy, hormonal therapies, and a variety of targeted therapies interact with each RT strategy. 

SBRT, Palliative RT, and Conventional RT

SBRT delivers high-dose radiation in a small number of fractions to localized targets, typically without surgery. Generally a standalone therapy, SBRT is used for small-volume, local targets, such as pancreatic, liver, or brain lesions. 

Palliative RT is intended to reduce or prevent symptoms and generally uses a lower dose per fraction over a relatively short treatment course. This broad category covers a range of clinical scenarios and treatment settings, with many systemic therapy decisions ultimately made on a case-by-case basis. 

Conventional RT can be a definitive treatment but is also often combined with surgery. This strategy uses a small dose per fraction over a long treatment course and can have varying target volumes, depending on the treatment setting. 

Cytotoxic Chemotherapy

Many cytotoxic chemotherapy agents are older, and most agents lack robust prospective data or detailed treatment guidelines on overlapping with RT, Dr. Sanford said. For SBRT, Dr. Sanford recommends holding cytotoxic chemotherapy 1 to 3 days before and after the RT course. For palliative RT, it’s best to hold chemotherapy for RT courses with large-volume or thoracic target fields. However, it may be appropriate to continue chemotherapy if the target field is small or in the extremities. For conventional RT, chemotherapy is often used concurrently as a radiosensitizing regimen, although separate cytotoxic chemotherapy treatment should be held. 

Immunotherapies, HER2 Monoclonal Antibodies, and Hormonal Therapies

Broadly, systemic treatment with immunotherapies, HER2–directed monoclonal antibodies, or hormonal agents can be safely continued during SBRT, palliative RT, or conventional RT. Specific data are emerging for incorporating conventional RT in consolidation strategies for patients with lung cancer on immunotherapy. However, given that many immunotherapy agents are associated with a risk of pneumonitis, continuing immunotherapy during RT may require more consideration for patients with pulmonary comorbidities or other risk factors, Dr. Sanford said. 

VEGF Inhibitors

Vascular endothelial growth factor (VEGF) inhibitors are associated with adverse effects, including GI perforation, poor wound healing, and increased bleeding, which may warrant holding depending on the radiation modality and target field. Oncologists should hold VEGF inhibitors during an SBRT course and consider a 1- to 2-week washout period. For palliative RT, VEGF inhibitors should be held if the target field includes the airway, esophagus, or bowel mucosa, whereas treatment can usually be continued for peripheral lung, extremity, bone, brain, and similar targets. Patients can generally continue systemic treatment during conventional RT, but holds may again be warranted for large-volume target fields in the airway, esophagus, or bowel.

Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitors (TKIs) should be held during and roughly 3 days before and after a course of SBRT. TKIs should similarly be held for a palliative RT course for large bowel or lung targets but are safe to continue for small targets. TKIs can generally be continued during conventional RT, although some retrospective data suggest there is increased toxicity in head and neck cancer populations, Dr. Sanford said.

BRAF Inhibitors

Continuing BRAF inhibitors during RT has been associated with risks for radiation dermatitis and GI tract or central nervous system (CNS) toxicity. Because BRAF inhibitors were developed more recently, these agents have some of the latest treatment guidelines in relation to RT, Dr. Sanford said. Doses should be held during and at least 3 days before and after palliative or conventional RT but held during and at least 1 day before and after SBRT, as the generally lower target field volumes have a lower risk of skin toxicity.

Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are a novel class of agents emerging as treatment options for several disease sites. Some evidence suggests combining ADCs with RT increases the risk of radionecrosis, but the data are sparse and often not restricted to symptomatic radionecrosis, Dr. Sanford said. Generally, she recommends holding ADCs 1 to 2 weeks before and during SBRT and waiting several days after before restarting. For palliative RT, oncologists should hold ADCs 1 week prior for high-risk CNS, lung, or bowel targets but may potentially continue ADCs for lower-risk sites. ADCs can usually be continued during conventional RT, although large CNS or thoracic targets again may warrant holding. 

CDK4/6 Inhibitors

CDK4/6 inhibitors are primarily used in breast cancer, and ongoing studies are evaluating concurrent CDK4/6 inhibitor therapy with RT modalities, Dr. Sanford said. Generally, doses should be held during and 3 to 7 days before and after SBRT or palliative RT with large bowel or bone marrow targets. For conventional RT, baseline neutropenia or large-volume bowel targeting may warrant holds, although reducing CDK4/6 inhibitor dose and RT fraction can allow many patients to overlap both treatments. 

PARP Inhibitors

Poly(ADP-ribose) polymerase (PARP) inhibitors are primarily approved for certain tumor types with BRCA1 or BRCA2 alterations. Notably, PARP inhibitors are used intentionally as a radiosensitizing agent alongside conventional RT to treat pancreas and ovarian cancer. Outside of this setting, PARP inhibitors should be held during and 1 to 3 days before and after SBRT, palliative RT, or conventional RT. 

Ultimately, these recommendations offer a conceptual outline for appropriate practices based on currently available evidence. Treatment decisions should always be individualized based on disease characteristics, comorbidities, and overall treatment strategy, Dr. Sanford said.