Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2023 Apr 28:13:1078915.
doi: 10.3389/fonc.2023.1078915. eCollection 2023.

PD-1 inhibitor combined with radiotherapy and GM-CSF in MSS/pMMR metastatic colon cancer: a case report

Jiabao Yang  1   2   3 , Pengfei Xing  1   2   3 , Yuehong Kong  1   2   3 , Meiling Xu  1   2   3 , Liyuan Zhang  1   2   3
Affiliations
Case Reports

PD-1 inhibitor combined with radiotherapy and GM-CSF in MSS/pMMR metastatic colon cancer: a case report

Jiabao Yang et al. Front Oncol. .

Abstract

Patients with chemo-refractory metastatic colorectal cancer (mCRC) have poor prognoses. The application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors encouragingly improved the survival of mCRC patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR). Unfortunately, it was ineffective for mCRC with microsatellite-stable (MSS)/proficient mismatch repair (pMMR), which accounted for 95% of mCRC. Radiotherapy can promote local control by directly killing tumor cells and inducing positive immune activities, which might help synergistically with immunotherapy. We present the report of an advanced MSS/pMMR mCRC patient who had progressive disease (PD) after first-line chemotherapy, palliative surgery and second-line chemotherapy combined with targeted therapy. Then the patient received the therapy of PD-1 inhibitor combined with radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF). According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), the patient showed a complete response (CR) after triple-combined therapy with progression-free survival (PFS) for more than 2 years so far. The patient had no other significant adverse reactions except for fatigue (Grade 1). The triple-combination therapy provided a promising strategy for metastatic chemo-refractory MSS/pMMR mCRC patients.

Keywords: GM-CSF; MSS/pMMR; case report; colorectal cancer; immunotherapy; radiotherapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) The PET-CT showed the high SUVmean of ascending colon and enlarged lymph nodes of retroperitoneal and peritoneal. (B) In a PRaG cycle, radiotherapy was delivered for metastases, followed by GM-CSF subcutaneous (sc) injection once daily for two weeks, and toripalimab was intravenous(iv) once within one week after radiotherapy. PRaG Therapy was repeated every three weeks, and three cycles of triple-therapy were administered. Subsequently, the patient underwent three cycles of PD-1 inhibotor and GM-CSF maintenance treatment.
Figure 2
Figure 2
CT scans before, during, and after the PRaG therapy. The CT scans (A, B) showed shrunk and disappeared of irradiated lymph node metastases. The CT scans (C) showed shrunk and disappeared of nonirradiated lymph node metastases. The arrows point to individual lymph nodes, and the circles include fusion lymph nodes.
Figure 3
Figure 3
(A) The carcinoembryonic antigen (CEA) dropped to the normal range after two cycles of PRaG Therapy. In the whole course of treatment, the patients had no obvious adverse reactions. Due to the influence of COVID-19, the re-examination interval was longer than expected. (B) The scheme shows the complete treatment process of the patient. (C) The number and activation of lymphocytes are related to the efficacy of immunotherapy.
See this image and copyright information in PMC

References

    1. Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA (2021) 325(7):669–85. doi: 10.1001/jama.2021.0106 - DOI - PubMed
    1. Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, et al. . Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-Deficient/Microsatellite instability-high metastatic colorectal cancer. J Clin Oncol (2018) 36(8):773–9. doi: 10.1200/JCO.2017.76.9901 - DOI - PubMed
    1. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. . PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med (2015) 372(26):2509–20. doi: 10.1056/NEJMoa1500596 - DOI - PMC - PubMed
    1. O'Neil BH, Wallmark JM, Lorente D, Elez E, Raimbourg J, Gomez-Roca C, et al. . Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. PloS One (2017) 12(12):e0189848. doi: 10.1371/journal.pone.0189848 - DOI - PMC - PubMed
    1. Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, et al. . Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest (2014) 124(2):687–95. doi: 10.1172/JCI67313 - DOI - PMC - PubMed

Publication types