Colorectal Cancer in Pediatric Patients: A Rare and Critical Concern

In the inaugural event of the Global Cancer Movement, initiated by OncoDaily, Dr. Amina Suleymanova, Pediatric Oncologist at the N.N. Blokhin National Medical Research Center of Oncology, highlighted the critical challenges and advancements in managing pediatric colorectal cancer. Held virtually from December 6-8, 2024, the event brought together global experts to address key issues in cancer care.

Dr. Amina’s presentation addresses the rare occurrence of colorectal cancer in pediatric patients, a condition that represents about 1% of all pediatric malignancies, with an incidence of approximately one case per million children. Despite its rarity, Dr. Amina highlights the clinical importance of understanding colorectal cancer in this demographic, as pediatric patients often present with advanced stages of the disease.

She references data from various studies to illustrate the distinct characteristics of colorectal cancer in children compared to adults, including more aggressive histological subtypes, particularly adenocarcinoma, and a higher proportion of left-sided colon cancer.

Drawing on the findings of the U.S. National Cancer Database, Dr. Amina notes that younger pediatric patients tend to have worse prognoses, especially those with rectal cancer, as age is identified as an independent negative prognostic factor. In contrast to adult patients, the younger pediatric population with colorectal cancer more often presents with advanced disease, and survival rates for stage 3 and 4 cancers are alarmingly low, with stage 4 patients surviving only 7% of the time.

A study from hospitals in Jude further supports these findings, reporting that 86% of pediatric cases were diagnosed at advanced stages, and that aggressive histology was a significant predictor of adverse outcomes. This emphasizes the importance of early detection and adequate surgical interventions, including proper nodal sampling, which can improve patient outcomes.

Further exploration of molecular profiling in pediatric colorectal cancer shows significant biological differences between pediatric and adult cancers. Dr. Amina highlights recent studies that suggest key mutations, such as RNF43 mutations and TP53 mutations, are more prevalent in pediatric patients. Additionally, pediatric colorectal cancers often involve the activation of the WNT signaling pathway through different mechanisms.

The presence of hereditary genetic syndromes, such as Lynch syndrome and familial adenomatous polyposis, is also more common in pediatric cases, with one study reporting 35% of pediatric colorectal cancer patients having hereditary syndromes. Interestingly, these patients tend to have better survival rates, as their disease is often more localized at the time of diagnosis.

Dr. Amina also shares data from her own center, where they treated 68 patients with adult-type gastrointestinal tumors over eight years, including 32 pediatric patients with colorectal cancer. The median age of diagnosis in this cohort was 13 years, and the most common symptoms were pain, nausea, vomiting, and rectal bleeding in cases of rectal cancer.

The distribution of the disease was predominantly left-sided colon cancer (50%), with a smaller percentage involving the right colon (25%) and rectum (14%). A significant portion of these patients presented with advanced stages of cancer, with 42% diagnosed at stage 3 and 35% at stage 4. Mucinosis and signet ring cell tumors were the most common histological types observed.

The molecular profile of these patients revealed a low frequency of RAS family mutations (16%), with only one patient showing RAS mutation. Additionally, microsatellite instability was detected in just 10% of cases. Treatment for these patients was multimodal, including surgery, chemotherapy, targeted therapy, and radiation for those with rectal cancer.

Dr. Amina emphasized the importance of molecular genetic profiling, using platforms like Foundation Medicine’s next-generation sequencing, to identify mutations such as TP53 and SMED4, which were present in 70% and 40% of patients, respectively. However, mutations typically associated with pediatric colorectal cancer, like PQC mutations, were rare in her cohort.

Dr. Amina also discussed the overall survival rates of the pediatric cohort, which were notably low, with an overall survival rate of 41% and event-free survival at 30%. Despite these challenges, she presented two clinical case studies showcasing successful treatments.

One involved a 16-year-old boy with metastatic adenocarcinoma of the descending colon, who responded well to immunotherapy (nivolumab and ipilimumab) after initial chemotherapy, leading to a complete response. Another case involved a 14-year-old boy with rectal adenocarcinoma, who responded favorably to combination chemotherapy and radiotherapy, ultimately undergoing surgery with complete therapeutic response.

In conclusion, Dr. Amina stresses the rarity and complexity of pediatric colorectal cancer and the need for continued collaborative research to improve therapeutic outcomes for this patient group. She asserts that current treatment approaches used for adult colorectal cancer are also applicable to pediatric patients, though further investigation is necessary to tailor therapies more specifically for the unique characteristics of pediatric tumors.