Managing Locally Advanced Rectal Cancer with Short-Course Radiation Therapy During the COVID-19 Pandemic

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The COVID-19 pandemic is consuming a significant amount of healthcare resources, especially in New York City, which became the global epicenter of the outbreak at the end of March 2020. Given the concerns around rapidly rising infection rates, impending staffing shortages, and the potential for the reallocation of resources, we evaluated our rectal cancer practice policies.

After careful consideration of the risks and benefits, the Colorectal Disease Management Team at Memorial Sloan Kettering Cancer Center (MSK) decided that all patients with locally advanced colorectal will be treated with short-course radiation therapy (SCRT) rather than standard long-course chemoradiation therapy (LCCRT). We have detailed our position in a paper published recently in Advances in Radiation Oncology(1)

Despite being more cost-effective than LCCRT, (2) SCRT has been employed in less than one percent of American patients undergoing neoadjuvant radiation for rectal cancer, in part due to strong biases among physicians regarding diminished downstaging and increased toxicity. (3)(4) We feel that these concerns merit re-evaluation since multiple randomized trials have demonstrated no differences in locoregional recurrence, distant recurrence, or overall survival between SCRT and LCCRT. (5)(6)(7)

Overall, SCRT is a well-validated alternative that limits the potential for patients and healthcare staff to contract COVID-19 and significantly reduces the utilization of healthcare resources. Moving to SCRT for all patients with locally advanced rectal cancer will allow us to meet the needs of more patients with potentially curable disease at a time when resources are severely constrained.

Overall, SCRT is a well-validated alternative that limits the potential for patients and healthcare staff to contract COVID-19 and significantly reduces the utilization of healthcare resources.
Paul Romesser

Long-Course Chemoradiation Therapy: The Standard Approach

Before March 2020, the standard approach for treating patients with locally advanced rectal cancer was total neoadjuvant therapy, which incorporated pre-operative LCCRT. (8)(9) Chemoradiation was given in 25 to 28 fractions using three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) with concurrent capecitabine. Our most common treatment approach was induction chemotherapy, followed by consolidative chemoradiation, (8) with the sequence of chemoradiation and chemotherapy altered depending on the clinical circumstances of individual cases.

At MSK, we questioned the utility of LCCRT in the setting of the COVID-19 pandemic due to concerns for increased opportunities for SARS-CoV-2 infection among patients and staff during prolonged and frequent visits and contingency planning issues that would arise with a reallocation of institutional resources.

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Evidence in Favor of Short-Course Radiation Therapy

SCRT is given in five fractions, using either 3D-CRT or IMRT, to protect neighboring healthy tissue. No concurrent chemotherapy is given with SCRT as the dose per fraction is higher than with LCCRT. Pre-operative radiation therapy has been shown to prevent locoregional recurrence in locally advanced rectal cancer with both SCRT (10)(11)(12) and LCCRT. (13)

In the absence of data from randomized controlled trials, some physicians have raised the concern that SCRT may result in less tumor downstaging, especially for patients with low rectal tumors < five cm from the anal verge, or bulky tumors with a close or involved circumferential resection margin. Another concern is a higher rate of late toxicity observed in patients with tumors abutting the anal canal. (7)(14)

However, in the Stockholm III trial, which evaluated SCRT with immediate surgery, SCRT with delayed surgery, and LCCRT with delayed surgery, researchers found no difference in locoregional recurrence, distant metastasis, or overall survival. There were greater tumor downstaging and higher acute toxicity, yet decreased surgical and post-operative complications among patients who had SCRT with delayed surgery compared to those who had SCRT with immediate surgery. (5)Further, a longer interval from radiation to surgery resulted in greater tumor downstaging for both SCRT, (5) which has also been demonstrated with LCCRT. (15)

Beyond the Stockholm III trial, two other randomized trials have also found no difference in locoregional recurrence, distant recurrence, or overall survival between these two radiation approaches. (6)(7)

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Benefits of SCRT During the COVID-19 Pandemic

The incorporation of SCRT into total neoadjuvant therapy has shown promising results in several clinical studies. (16)(17)(18)(19)(20) While it is still under ongoing investigation, our Colorectal Disease Management Team concluded it is both reasonable and necessary to give total neoadjuvant therapy with SCRT off-trial given the issues and constraints with the ongoing COVID-19 pandemic.

In the setting of the COVID-19 pandemic, we believe SCRT will:

  1. Provide efficient and quality oncologic care for our patients

  2. Significantly decrease patient exposure to potential SARS-CoV-2 infection compared to more frequent and more prolonged visits for LLCRT

  3. Decrease the likelihood of a patient being diagnosed with COVID-19 during treatment

  4. Decrease immunosuppression as concurrent chemotherapy is omitted

  5. Decrease resource utilization in a setting where the capacity to deliver radiotherapy may be significantly curtailed

  6. Provide at least partial therapy when surgery and/or chemotherapy need to be delayed

  7. Reinforce federal, state, and city mandates that encourage physical distancing while still treating patients with active cancers

Moving to SCRT over LCCRT benefits patients by reducing their exposures to other potentially infected patients and healthcare workers and lowers the chance of treatment interruption or termination if they were to be diagnosed with COVID-19.

This new direction is also in the best interest of all patients at MSK. Decreased utilization of healthcare resources with SCRT will mean that we can treat five patients instead of one during the pandemic, a time when we expect to have substantial reductions in staffing due to healthcare workers becoming sick with the novel coronavirus.

The information presented above represents the collective views of the authors and does not represent an institutional position. Authors on the paper include: Paul Romesser, MD; Abraham J. Wu, MD; Andrea Cercek MD; J. Joshua Smith, MD, PhD, FACS; Martin Weiser, MD; Leonard Saltz, MD; Julio Garcia-Aguilar, MD, PhD; and Christopher H. Crane, MD.

Dr. Romesser reports research funding from and is a consultant for EMD Serono and has received travel support from Elekta. Dr. Wu reports research funding from CivaTech Oncology, personal fees from AstraZeneca, and non-financial support from AlphaTau Medical. Dr. Cercek reports research funding from Tesaro/ GSK, Seattle Genetics, and RGenix, and personal fees from Array Biopharma and Bayer. Dr. Garcia-Aguilar reports personal fees from Medtronic, Johnson and Johnson, and Intuitive Surgical.

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  1. Romesser PB, Wu AJ, Cercek A, et al. Management of Locally Advanced Rectal Cancer During The COVID-19 Pandemic: A Necessary Paradigm Change at Memorial Sloan Kettering Cancer Center [published online ahead of print, 2020 Apr 22]. Adv Radiat Oncol. 2020;10.1016/j.adro.2020.04.011.

  2. Raldow A.C. Cost-effectiveness of Short-Course Radiation Therapy vs Long-Course Chemoradiation for Locally Advanced Rectal Cancer. JAMA Netw Open. 2019;2(4):e192249.

  3. Sineshaw H.M., Jemal A., Thomas C.R., Jr., Mitin T. Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: An analysis from the National Cancer Data Base. Cancer. 2016;122:1996–2003.

  4. Mowery Y.M. Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States. Cancer. 2017;123:1434–1441.

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  7. Ngan S.Y. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans- Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012;30:3827–3833.

  8. Cercek A. Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol. 2018;4(6):e180071.

  9. Smith J.J. Assessment of a Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After Neoadjuvant Therapy. JAMA Oncol. 2019;5(4):e185896.

  10. Folkesson J. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005;23:5644–5650.

  11. van Gijn W. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12:575–582.

  12. Sebag-Montefiore D. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–820.

  13. Sauer R. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–1740.

  14. Downing A. Functional Outcomes and Health-Related Quality of Life After Curative Treatment for Rectal Cancer: A Population-Level Study in England. Int J Radiat Oncol Biol Phys. 2019;103:1132–1142.

  15. Garcia-Aguilar J. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957–966.

  16. Myerson R.J. Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. Int J Radiat Oncol Biol Phys. 2014;88:829–836.

  17. Bujko K. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016;27:834–842.

  18. Jia A.Y. Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma. Radiat Oncol. 2019;14:147.

  19. Markovina S. Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis. Int J Radiat Oncol Biol Phys. 2017;99:417–426.

  20. van der Valk M.J.M. Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial. Radiother Oncol. 2020;147:75–8