Complete response to pembrolizumab in a paediatric patient with Lynch syndrome-associated colorectal cancer: a case report and review of immunotherapy-related bowel obstruction.

内容摘要

Colorectal cancer (CRC) is extremely rare in paediatrics with aggressive histopathology and advanced presentation. Whilst pembrolizumab has shown efficacy in adult microsatellite instability-high or mismatch repair deficiency CRC, paediatric data remain scarce. A 12-year- old boy with Lynch syndrome-associated CRC developed severe cardiac toxicity after initial chemotherapy. Treatment was switched to off-label pembrolizumab, resulting in a complete response after 24 cycles. Despite good tolerability, the patient developed a delayed bowel stricture at the tumour site. After surgery, there was no pathological evidence of residual adenocarcinoma. This case demonstrates the potential of pembrolizumab in paediatric CRC, highlighting the importance of molecular-guided rather than age-restricted therapy selection. Colorectal cancer (CRC) is exceptionally rare in children and adolescents. When it does occur at a young age, it is often linked to inherited genetic conditions. Lynch syndrome is one such condition, caused by inherited faults in genes responsible for correcting errors in DNA replication. Patients with Lynch syndrome carry a substantially elevated lifetime risk of developing CRC and other cancers. This article presents the case of a 12-year-old boy diagnosed with Lynch syndrome-associated CRC. Molecular analysis of his tumour revealed a profile known as microsatellite instability-high (MSI-H) and mismatch repair deficiency (dMMR). Standard chemotherapy was started but had to be discontinued after the first cycle, when the patient developed serious heart toxicity. Faced with this situation, the multidisciplinary team decided to use pembrolizumab, a monoclonal antibody targeting PD1. Pembrolizumab is approved for MSI-H/dMMR CRC in adults but was used here off-label, as no approved indication exists for children in Italy. After 24 treatment cycles, the patient achieved a complete response: all detectable tumour activity resolved, and biopsies of residual lymph nodes confirmed the absence of cancer. The treatment was generally well tolerated. However, approximately 1 year after completing immunotherapy, the patient developed a severe narrowing (stricture) of the bowel at the site where the tumour had been. This complication — believed to result from scarring as the tumour regressed — has been rarely described in adults following immunotherapy, but this is the first reported case in a paediatric patient. Surgical removal of the affected bowel segment was performed, and pathological examination confirmed no residual cancer. The patient remains without cancer more than 2 years later. This case carries important messages for patients and clinicians. Tumour biology — not patient age — should guide treatment selection for young people with CRC. Off-label immunotherapy can be considered in MSI-H/dMMR paediatric CRC when standard options are unavailable or not tolerated. Clinicians should be aware that bowel obstruction may occur as a delayed complication of successful immunotherapy, even in children. Finally, expanding access to clinical trials for paediatric oncology patients remains an urgent priority to ensure that younger patients benefit equally from advances in cancer treatment.