Journal Club Radiation Biology

Immunotherapy, Radiation, and Breast Cancer

Ian Pereira and Hina Saeed

Advances in systemics and radiation treatment techniques have mirrored improved cancer control worldwide.  Recently, the exponential use of newer immunotherapies, implicated in upregulating immune system, has improved survival for patients across a growing list of cancers including melanoma and lung cancer.  Radiation treatment, which is often used with traditional systemics, has the potential to benefit over 50% of cancer patients.1,2 Similarly, increasing adoption of newer locally ablative techniques such as stereotactic body radiation therapy (SBRT) for limited burden metastatic disease has shown promising survival signals with limited toxicities.3  

Our improved understanding of tumor biology has shown that both immunotherapy and SBRT alter the tumor microenvironment (TME).  With both modalities greatly contributing to a new hope in advanced cancer control, it is not surprising that their courtship is increasingly considered. However, despite their liquid gold or silver bullet mainstream appearance, our knowledge of the right patient, right time, right sequence and right cost is still limited – these advances may not be for everyone.4


Breast cancer is the most commonly diagnosed cancer in women and a leading cause of cancer death worldwide. Despite gains due to improved screening and increased access to and quality of surgery, traditional systemics, and radiation treatment, increasing incidence and burden of disease is driving higher demand for better treatments. Impassioned work5 and keynotes6 led to recent immunotherapy approvals in advanced breast cancer. A historically rarely seen “abscopal effect”, described from the 1950s where radiation was thought to systemically affect cancer cells outside the treated area, is increasingly witnessed in ImmunoRT combinations for breast cancer.  

The “potentially” curable oligometastatic state in breast cancer has spurred more routine use of locally ablative techniques for systemic disease outside of clinical trials.  This presents both opportunities and challenges for the study and use of immunotherapy & radiation treatment (ImmunoRT) combinations, and early evidence is growing in areas including the TME, radiation treatment techniques, and biomarkers of response.

The October Radiation Oncology Journal Club is going to be a recent review on ImmunoRT to help understand the current state of this combination and the next steps to improve our outcomes, globally:

            Ho AY, Wright JL, Blitzblau RC, et al. Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists. International Journal of Radiation Oncology*Biology*Physics. 2020;108(1):227-241.


Special thanks to Dr. Alice Ho (@AliceHoMD) and other co-authors who will be joining the journal club (#radonc #jc) this weekend, from at 8 am CST Saturday, October 17 until the live hour from 1-2 pm CST Sunday, October 18.  We also thank the Red Journal for making the article free to download here to encourage more equitable participation.

To help guide the discussion, we will discuss the following topics:

T1: What is the background of this paper?  Why is a better understanding of immunotherapies and their combination with radiation treatment (ImmunoRT) important?


T2: What was the methodology of this study? Why and how were particular ImmunoRT domains chosen? Were any relevant domains that were not included? What was the quality of the included studies?

T3: What were the results of this paper?  In which global populations may it apply? Are there any considerations from a health equity, diversity, and inclusion lens?

T4: Are the benefits for ImmunoRT worth the harms including financial toxicity?

T5: What can be done to improve the use of and outcomes for ImmunoRT locally, regionally, and globally?

We welcome you join us in unlearning and learning, together, towards improving outcomes for ImmunoRT.

Need more information?

  • To get started – Here are guidelines on how to participate and our disclaimer for ways to keep the experience rewarding and professional. If you’re not ready, just lurk and tune into the conversation.
  • Feel free to add the respective diseases site tags to your tweets (i.e. Breast Cancer and Social Media – #bcsm; Immunotherapy & Radiation Treatment – #ImmunoRT; Radiobiology – #Radbio; Radiation Oncology Education – #ROEdu). This facilitates online knowledge-sharing with the appropriate cancer community. Just don’t forget the #radonc #jc tags!

Any suggestions? Leave a comment or tweet us at @Rad_Nation.
Looking forward to seeing everyone, virtually, this weekend!


References:

1.         Barton MB, Frommer M, Shafiq J. Role of radiotherapy in cancer control in low-income and middle-income countries. Lancet Oncol. 2006;7(7):584-595.

2.         Tyldesley S, Delaney G, Foroudi F, Barbera L, Kerba M, Mackillop W. Estimating the need for radiotherapy for patients with prostate, breast, and lung cancers: verification of model estimates of need with radiotherapy utilization data from British Columbia. Int J Radiat Oncol Biol Phys. 2011;79(5):1507-1515.

3.         Palma DA, Olson R, Harrow S, et al. Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. Journal of Clinical Oncology. 2020:JCO.20.00818.

4.         Haslam A, Gill J, Prasad V. Estimation of the Percentage of US Patients With Cancer Who Are Eligible for Immune Checkpoint Inhibitor Drugs. JAMA Network Open. 2020;3(3):e200423-e200423.

5.         Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. 2018;379(22):2108-2121.

6.         Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. New England Journal of Medicine. 2020;382(9):810-821.

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