Oxaliplatin, irinotecan, and 5-fluorouracil in combination with or without targeted therapies are now well-documented treatment options for first- and second-line treatments of metastatic colorectal cancer. Furthermore, many guidelines regard these treatment options as the standard of care of the disease. However, there is much less data on the beneficial effect of salvage systemic therapy. Therefore, salvage treatment for patients with metastatic colorectal cancer after the use of approved drugs or their combinations is reviewed here. Conventional chemotherapeutic agents such as capecitabine, mitomycin C, and gemcitabine have limited or no activity when used as salvage treatment. Antiangiogenic drugs may postpone further progression and prolong survival. Regorafenib and TAS-102 have been established as salvage therapy agents. Further prospective phase III trials comparing an investigational drug alone or in combination with best supportive care as third- or later lines of treatment in metastatic colorectal cancer are highly warranted. Moreover, it is crucial to identify predictive biomarkers and improve our understanding of molecular mechanisms.
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Ann Surg Oncol
January 2025
Department Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
Background: Anastomotic leakage (AL) is a major complication in colorectal surgery, particularly following rectal cancer surgery, necessitating effective prevention strategies. The increasing frequency of colorectal resections and anastomoses during cytoreductive surgery (CRS) for peritoneal carcinomatosis further complicates this issue owing to the diverse patient populations with varied tumor distributions and surgical complexities. This study aims to assess and compare AL incidence and associated risk factors across conventional colorectal cancer surgery (CRC), gastrointestinal CRS (GI-CRS), and ovarian CRS (OC-CRS), with a secondary focus on evaluating the role of protective ostomies.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background: Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Background: Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy.
View Article and Find Full Text PDFClin Exp Med
January 2025
Liver & Peritonectomy Unit, Department of Surgery, St George Hospital, Pitney Building, Short Street, Kogarah, NSW, 2217, Australia.
Purpose: This study seeks to resolve a fundamental question in oncology: Why do appendiceal and colorectal adenocarcinomas exhibit distinct liver metastasis rates? Building on our prior hypothesis published in the British Journal of Surgery, our institution has investigated potential DNA mutations within the carcinoembryonic antigen-related cell adhesion molecule (CEACAM5) gene's Pro-Glu-Leu-Pro-Lys (PELPK) motif to evaluate its role as a biomarker for liver metastasis risk.
Methods: Partnering with the Australian Genome Research Facility, the PELPK motif of CEACAM5 was analysed in colorectal and appendiceal adenocarcinomas to detect DNA mutations associated with liver metastasis. Additionally, our institution performed the COPPER trial to assess carcinoembryonic antigen (CEA) levels in portal versus peripheral blood in patients with appendiceal adenocarcinoma and a systematic review and meta-analysis of 136 studies on CEA's prognostic significance among patients with colorectal and appendiceal adenocarcinoma.
Br J Cancer
January 2025
Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: This study aimed to investigate the prognostic impact of lymph node metastasis (LNM) on patients with colorectal cancer liver metastasis (CRLM) and elucidate the underlying immune mechanisms using multiomics profiling.
Methods: We enrolled patients with CRLM from the US Surveillance, Epidemiology, and End Results (SEER) cohort and a multicenter Chinese cohort, integrating bulk RNA sequencing, single-cell RNA sequencing and proteomics data. The cancer-specific survival (CSS) and immune profiles of the tumor-draining lymph nodes (TDLNs), primary tumors and liver metastasis were compared between patients with and without LNM.
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