The effect of immunotherapy in a young patient with mismatch repair-deficient rectal cancer – a case report
Authors:
T. Sokop; R. Obermannová
Authors‘ workplace:
Klinika komplexní onkologické péče LF MU a MOÚ Brno
Published in:
Klin Onkol 2023; 36(3): 241-245
Category:
Case Report
doi:
https://doi.org/10.48095/ccko2023241
Overview
Background: The incidence of colorectal cancer (CRC) in the age group of young patients has been increasing. Furthermore, in these patients, CRC is more frequently an aggressive histological type of tumor, diagnosed in the late clinical stages of the disease. Another characteristic feature is a higher frequency of mismatch repair deficient (dMMR) tumors, in the treatment of which immunotherapy can be an effective treatment modality, used to prolong overall survival and improve quality of life. Conversely, the effect of chemotherapy may be lower. Case: We present the case of a 35year-old patient treated with primary therapy for locally advanced dMMR rectal cancer. Neoadjuvant chemoradiotherapy was followed by rectal resection, which was accompanied by serious postoperative complications. In addition, there was an early local relapse of the disease, resistant to systemic chemotherapy treatment. After the progression of the disease, second line of the treatment with pembrolizumab was initiated. Results: The treatment with pembrolizumab led to a partial regression of the disease and subsequently its stabilization, which has been lasting for 15 months. The improvement of the patient‘s quality of life, e. g. stabilization of the blood count and regression of diarrhea, is a significant benefit. In addition, the treatment has been given without the development of serious toxicity, so far. Conclusion: Microsatellite instability testing in the management of locally advanced and metastatic colorectal cancer is of fundamental importance in setting the appropriate treatment procedures. In the future, we can expect results of several studies that will try to prove the effect of immunotherapy not only in metastatic disease, but also in the neoadjuvant regimen in resectable and potentially resectable dMMR rectal and colon cancers.
Keywords:
colorectal cancer – immunotherapy – pembrolizumab – young adult – immune checkpoint inhibitor
Sources
1. ÚZIS. Novotvary 2018 – současné epidemiologické trendy novotvarů v České republice. [online]. Dostupné z: https: //www.uzis.cz/res/f/008352/novotvary2018.pdf.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69 (1): 7–34. doi: 10.3322/caac.21551.
3. Siegel RL, Torre LA, Soerjomataram I et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut 2019; 68 (12): 2179–2185. doi: 10.1136/ gutjnl-2019-319511.
4. Stoffel EM, Murphy CC. Epidemiology and mechanisms of the increasing incidence of colon and rectal cancers in young adults. Gastroenterology 2020; 158 (2): 341–353. doi: 10.1053/j.gastro.2019.07.055.
5. Holowatyj AN, Lewis MA, Pannier ST et al. Clinicopathologic and racial/ethnic differences of colorectal cancer among adolescents and young adults. Clin Transl Gastroenterol 2019; 10 (7): e00059. doi: 10.14309/ctg.0000 000000000059.
6. Rodriguez L, Brennan K, Karim S et al. Disease characteristics, clinical management, and outcomes of young patients with colon cancer: a population-based study. Clin Colorectal Cancer 2018; 17 (4): e651–e661. doi: 10.1016/ j.clcc.2018.06.007.
7. Weinberg BA, Marshall JL. Colon cancer in young adults: trends and their implications. Curr Oncol Rep 2019; 21 (1): 3. doi: 10.1007/s11912-019-0756-8.
8. Tricoli JV, Boardman LA, Patidar R et al. A mutational comparison of adult and adolescent and young adult (AYA) colon cancer. Cancer 2018; 124 (5): 1070–1082. doi: 10.1002/cncr.31136.
9. Cheong C, Oh SY, Kim YB et al. Differences in biological behaviors between young and elderly patients with colorectal cancer. PLoS One 2019; 14 (6): e0218604. doi: 10.1371/journal.pone.0218604.
10. Chang C-C, Lin P-C, Lin C-C et al. Molecular and clinicopathological differences by age at the diagnosis of colorectal cancer. Int J Mol Sci 2017; 18 (7): 1441. doi: 10.3390/ijms18071441.
11. Pearlman R, Frankel WL, Swanson B et al. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol 2017; 3 (4): 464. doi: 10.1001/jamaoncol.2016.5194.
12. Durhuus JA, Therkildsen C, Kallemose T et al. Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study. BMJ Open 2021; 11 (12): e053538. doi: 10.1136/bmjopen-2021-053538.
13. Glynne-Jones R, Wyrwicz L, Tiret E et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017; 28 (Suppl 4): iv22–iv40. doi: 10.1093/annonc/mdx224.
14. Cervantes A, Adam R, Roselló S et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34 (1): 10–32. doi: 10.1016/j.annonc.2022.10.003.
15. ČLS JEP. Modrá kniha České onkologické společnosti. 28. aktualizace. Brno: Masarykův onkologický ústav 2022.
16. Chalabi M, Verschoor YL, van den Berg J et al. LBA7 – neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: the NICHE-2 study. Ann Oncol 2022; 33 (Suppl 7): S808–S869. doi: 10.1016/annonc/annonc1089.
17. Andre T, Amonkar M, Norquist JM et al. Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial. Lancet Oncol 2021; 22 (5): 665–677. doi: 10.1016/S1470-2045 (21) 00064-4.
18. Cercek A, Lumish M, Sinopoli J et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022; 386 (25): 2363–2376. doi: 10.1056/ NEJMoa2201445.
19. NCCN. Rectal Cancer (Version 3.2022). [online]. Available from: https: //www.nccn.org/professionals/physician_gls/pdf/rectal.pdf.
20. Cercek A, Dos Santos Fernandes G, Roxburgh CS et al. Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy. Clin Cancer Res 2020; 26 (13): 3271–3279. doi: 10.1158/1078-0432.CCR-19-3728.
21. Chalabi M, Fanchi LF, Dijkstra KK et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med 2020; 26 (4): 566–576. doi: 10.1038/s41591-020-0805-8.
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Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2023 Issue 3
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