Pembrolizumab and other immunotherapies have become central in treating metastatic colon cancer, particularly effective in patients with mismatch repair deficiencies. We report a case involving a man who initially underwent radical surgery for sigmoid colon cancer on April 27, 2011, followed by hepatic tumor resection on September 21, 2017. Post-surgery, he received eight cycles of adjuvant chemotherapy with the CAPEOX regimen and was regularly monitored through CT and MRI scans. On August 24, 2022, liver metastases were detected, and he was diagnosed with Lynch syndrome (LS) due to germline mutation in the MSH2 and EPCAM genes. He commenced treatment with 200mg of pembrolizumab intravenously every three weeks on September 2, 2022, and demonstrated a sustained response. However, after 17 cycles, he developed a treatment related adverse event (TRAE) of pancreatic endocrine dysfunction, leading to type 1 diabetes, managed with subcutaneous insulin injections. After 30 cycles of treatment, no evidence of disease was observed. This case underscores the significant clinical benefits of first-line pembrolizumab in managing hepatic metastasis in colonic carcinoma associated with LS, despite the occurrence of TRAEs. It raises critical questions regarding the optimal duration of immunotherapy following a complete or partial response and whether treatment should be discontinued upon the emergency of TRAEs. Continued research and forthcoming clinical trials with checkpoint inhibitors are expected to refine treatment protocols for LS-associated carcinoma.

Anti-programmed cell death protein 1 (PD-1) therapy has demonstrated notable efficacy in treating patients with deficient mismatch repair/high microsatellite instability (dMMR/MSI-H) metastatic colorectal cancer (mCRC). However, its clinical application is fraught with challenges and can lead to significant immune-related adverse events (ir-AEs). In this report, we present a complicated case of an mCRC patient with MSI-H and mutations in β2M and LRP1B proteins, complicated by concurrent bacteremia and liver fluke infection, who received first-line anti-PD1 therapy. The patient exhibited a positive response to anti-PD1 treatment, even in the presence of concomitant antibiotic and anti-parasitic interventions. Additionally, the patient experienced immunotherapy-related autoimmune hemolytic anemia (ir-AIHA), a rare hematological ir-AE, which was effectively treated later on. Immunotherapy represents a pivotal and highly effective approach to tumor treatment. Baseline assessment of the MMR and MSI status is a crucial step before initiating immunotherapy, and regular ongoing assessments during the treatment course can facilitate early recognition of any secondary complications, enabling prompt intervention and ensuring optimal therapeutic outcomes. Overall, a multidisciplinary diagnostic and therapeutic algorithm can help maximize the therapeutic benefits of immunotherapy.

Primary adenocarcinomas represent a small percentage of sinonasal malignancies. Metastasis of colorectal malignancies to the paranasal sinuses is rare, poorly understood, and typically fatal. This case documents an unusual source of metastatic sinonasal malignancy and offers comparison to a cohort of similar patients found in the literature.

OBJECTIVE: The value of upfront primary tumor resection (PTR) for asymptomatic unresectable metastatic colorectal cancer (mCRC) patients remains contentious. This meta-analysis aimed to assess the prognostic significance of upfront PTR for asymptomatic unresectable mCRC.
METHODS: A systematic literature search was performed on June 21st, 2024. To minimize the bias and ensure robust evidence, only randomized controlled trials (RCTs) and case-matched studies (CMS) that compared PTR followed by chemotherapy to chemotherapy alone were included. The primary outcome was overall survival (OS), while cancer-specific survival (CSS) served as the secondary outcome.
RESULTS: Eight studies (three RCTs and five CMS) involving 1221 patients were included. Compared to chemotherapy alone, upfront PTR followed by chemotherapy did not improve OS (hazard ratios [HR] 0.91, 95% confidence interval [CI] 0.79-1.04, P = 0.17), but was associated with slightly better CSS (HR 0.59, 95% CI 0.40-0.88, P = 0.009).
CONCLUSIONS: The current limited evidence indicates that upfront PTR does not improve OS but may enhance CSS in asymptomatic unresectable mCRC patients. Ongoing trials are expected to provide more reliable evidence on this issue.

BACKGROUND: BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment.
METHODS: Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead.
CONCLUSIONS: This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.

Liquid biopsies can accurately identify molecular alterations in patients with colorectal cancer with high concordance with tissue analysis and shorter turnaround times. Circulating tumor (ct) DNA analysis can be used for diagnosing and monitoring tumor evolution in patients with metastatic colorectal cancer who are treated with EGFR inhibitors. In this article, we reported three clinical cases to illustrate the relevance of RAS mutations identified in ctDNA samples of patients with wild-type metastatic colorectal cancer who received an EGFR inhibitor plus chemotherapy as first-line treatment. The identification of RAS mutations in these patients is one of the most frequently identified mechanisms of acquired resistance. However, detecting a KRAS mutation via liquid biopsy can be caused by inter-tumor heterogeneity or it can be a false positive due to clonal hematopoiesis. More research is needed to determine whether ctDNA monitoring may help guide therapy options in metastatic colorectal cancer patients. We performed a literature review to assess the technologies that are used for analysis of RAS mutations on ctDNA, the degree of agreement between tissue and plasma and the importance of tissue/plasma discordant cases.

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UNASSIGNED: Although long-term survival in patients with metastatic colorectal cancer (mCRC) is limited, treatments for third-line and later treatment are now recommended. We describe a patient who achieved long-term survival when they received third-line treatment with trifluridine/tipiracil (FTD/TPI).
UNASSIGNED: The woman who was 52 years old at diagnosis of adenocarcinoma of the right colon (T3/N0/M1) with metastases to the lung, liver, ovary, and other soft tissues received first-line fluoropyrimidine-based chemotherapy (FOLFOX/FOLFIRI plus bevacizumab) intermittently for approximately 8.5 years with generally stable disease, and second-line FOLFIRI plus radiotherapy. After progression on second-line therapy, the patient initiated treatment with FTD/TPI 35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. She received a total of 38 cycles of FTD/TPI over a period of 34 months achieving a partial response, maintained performance status, and improved quality of life. Neutropenia was successfully managed with FTD/TPI dose delays or reductions.
UNASSIGNED: This heavily pre-treated patient with mCRC demonstrated impressive long-term survival and maintenance of good quality of life with FTD/TPI treatment.

OBJECTIVE: The case of a 47-year-old female patient who underwent sigmoidectomy for metastatic colorectal cancer is reported. Treatment with capecitabine and 5-fluorouracil induced severe hypertriglyceridemia repeatedly.
METHODS: Based on laboratory tests and clinical evaluations, treatment was suggested by specialists.
RESULTS: After treatment with capecitabine, the patient\'s triglycerides increased from 19.7 mmol/L to 42 mmol/L. It was proposed that the patient had multifactorial chylomicronemia syndrome triggered by secondary factors. Statins, fenofibrate, ezetimib, and metformin were added to the therapy. After metastases appeared, FOLFIRI (leucovorin calcium [folinic acid], 5-fluorouracil, and irinotecan hydrochloride) chemotherapy and biological treatment (cetuximab) followed and triglycerides increased to 55.3 mmol/L.
CONCLUSIONS: Monitoring triglyceride levels before and during therapy is suggested.

BACKGROUND: Colorectal cancer (CRC) frequently involves mutations in the KRAS gene, impacting therapeutic strategies and prognosis. The occurrence of KRAS mutations typically precludes the presence of RET fusions, with current medical literature suggesting a mutual exclusivity between these two genetic alterations. We present a unique case that challenges this notion.
METHODS: An 85-year-old female with metastatic CRC was found to have a combination of genetic anomalies that is to the best of our knowledge not yet described in the medical literature: a KRAS p.G12C mutation, associated with oncogenesis and treatment resistance, and an ANK3::RET fusion, an infrequent but targetable mutation in CRC. This molecular profile was uncovered through comprehensive genomic sequencing after the patient experienced metachronous tumor dissemination. The presence of both genetic events complicates the treatment approach.
CONCLUSIONS: The identification of both a KRAS p.G12C mutation and an ANK3::RET fusion in the same CRC patient adds a new layer to the oncogenic landscape and treatment considerations for CRC. It highlights the intricate decision-making required in the era of precision medicine, where targeted therapies must be carefully chosen and potentially combined to combat complex genetic profiles. The case emphasizes the urgency of investigating the clinical effects of concurrent or sequential use of KRAS p.G12C and RET inhibitors to inform future therapeutic guidelines and improve patient outcomes in similar cases.