Neoadjuvant immunotherapy in a locally advanced colon cancer patient with MSI-H and suspected Lynch syndrome: A case report

Abstract

Carrilizumab, a PD-1 inhibitor, has shown therapeutic effectiveness in patients with late-stage or metastatic solid tumors exhibiting DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). dMMR/MSI-H cancer patients are known to be responsive to PD-1 inhibitors. However, the use of carrilizumab for preoperative immunotherapy in early, unresectable MSI-H/dMMR primary colon cancer lesions is relatively underexplored. We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient’s family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient’s symptoms resolved, and physical examination revealed no abdominal tenderness or palpable masses. Following radical colectomy, the primary tumor exhibited a pathological complete response. This case highlights the potential of preoperative neoadjuvant immunotherapy to improve staging accuracy and increase surgical resection rates in T4b MSI-H colon cancer patients without distant metastasis, suggesting a need for reconsideration of the treatment approach.

Zusammenfassung

Carrilizumab, ein PD-1-Inhibitor, hat sich bei Patienten mit soliden Tumoren im Spätstadium oder mit Metastasen, die einen Mangel an DNA-Mismatch-Reparatur (dMMR) oder eine hohe Mikrosatelliteninstabilität (MSI-H) aufweisen, als therapeutisch wirksam erwiesen. dMMR/MSI-H-Krebspatienten sprechen bekanntermaßen gut auf PD-1-Inhibitoren an. Der Einsatz von Carrilizumab zur präoperativen Immuntherapie bei frühen, inoperablen MSI-H/dMMR-Kolonkarzinom-Primärläsionen ist jedoch noch relativ wenig erforscht. Wir stellen den Fall eines 46-jährigen Mannes vor, der sich wegen einer zweiwöchigen Hämatochezie, einwöchigen rechtsseitigen Bauchschmerzen und eines lockeren Stuhlgangs in unserer Einrichtung vorstellte. Die Bildgebung wies auf eine Beteiligung des Zwölffingerdarms hin, und eine Biopsie bestätigte ein Adenokarzinom des aufsteigenden Dickdarms mit MSI-H-Status. Da in der Familie des Patienten über zwei Generationen hinweg mehr als drei bestätigte Fälle von Darmkrebs aufgetreten waren, wurde das Lynch-Syndrom in Betracht gezogen. Nach vier Zyklen einer PD-1-Antagonisten-Immuntherapie mit Carrilizumab klangen die Symptome des Patienten ab, und bei der körperlichen Untersuchung wurden keine abdominalen Schmerzen oder tastbare Massen festgestellt. Nach der radikalen Kolektomie zeigte der Primärtumor ein pathologisch vollständiges Ansprechen. Dieser Fall unterstreicht das Potenzial der präoperativen neoadjuvanten Immuntherapie zur Verbesserung der Staging-Genauigkeit und zur Erhöhung der chirurgischen Resektionsraten bei T4b MSI-H-Darmkrebspatienten ohne Fernmetastasen, was auf die Notwendigkeit eines Überdenkens des Behandlungsansatzes hinweist.

Keywords

Colon cancer - Neoadjuvant therapy - Immunotherapy - Microsatellite Instability-High - Deficient mismatch repair - case report

Schlüsselwörter

Darmkrebs - Neoadjuvante Therapie - Immuntherapie - Mikrosatelliteninstabilität - mangelhafte Fehlanpassungsreparatur - Fallbericht

Publikationsverlauf

Eingereicht: 05. Dezember 2023

Artikel online veröffentlicht:
11. April 2024

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