Chemotherapy and Surgery in Colon Cancer: for Better Treatment Outcomes

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Background: Personalized and novel evidence-based clinical treatment strategy consulting for colorectal cancer has been available through various artificial intelligence (AI) supporting systems such as Watson for Oncology (WFO) from IBM. However, the potential effects of this supporting tool in cancer care have not been thoroughly explored in real-world studies. This research aims to investigate the concordance between treatment recommendations for colorectal cancer patients made by WFO and a multidisciplinary team (MDT) at a major comprehensive gastrointestinal cancer center.

Methods: In this prospective study, both WFO and the blinded MDT’s treatment recommendations were provided concurrently for enrolled colorectal cancers of stages II to IV between March 2017 and January 2018 at Shanghai Minimally Invasive Surgery Center. Concordance was achieved if the cancer team’s decisions were listed in the “recommended” or “for consideration” classification in WFO. A review was carried out after 100 cases for all non-concordant patients to explain the inconsistency, and corresponding feedback was given to WFO’s database. The concordance of the subsequent cases was analyzed to evaluate both the performance and learning ability of WFO.

Results: Overall, 250 patients met the inclusion criteria and were recruited in the study. Eighty-one were diagnosed with colon cancer and 189 with rectal cancer. The concordances for colon cancer, rectal cancer, or overall were all 91%. The overall rates were 83, 94, and 88% in subgroups of stages II, III, and IV. When categorized by treatment strategy, concordances were 97, 93, 89, 87, and 100% for neoadjuvant, surgery, adjuvant, first line, and second line treatment groups, respectively. After analyzing the main factors causing discordance, relative updates were made in the database accordingly, which led to the concordance curve rising in most groups compared with the initial rates.

Conclusion: Clinical recommendations made by WFO and the cancer team were highly matched for colorectal cancer. Patient age, cancer stage, and the consideration of previous therapy details had a significant influence on concordance. Addressing these perspectives will facilitate the use of the cancer decision-support systems to help oncologists achieve the promise of precision medicine.

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(A, B) The survival curves showed that the MAC of RCC patients in the RHC group had similar OS and CSS as the PC group when sub-stratified by age (A, B), CEA level (C, D), PNI (E, F), differentiation (G, H) and TNM stage (I–L).
Original Research
01 February 2021

Background: The extent of bowel resection is widely debated in colon cancer surgery. Right hemicolectomy (RHC) and partial colectomy (PC) are the most common operation options for right-sided colon cancer (RCC). However, there are still no treatment guidelines or published studies to guide surgical options for mucinous adenocarcinoma (MAC) of RCC.

Methods: Patients with MAC and non-specific adenocarcinoma (AC) of RCC who underwent RHC and PC from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were retrieved. The general characteristics and survival were compared and analyzed.

Results: A total of 27,910 RCC patients were enrolled in this study, among them 3,413 were MAC. The results showed that race, carcinoembryonic antigen (CEA) level, perineural invasion (PNI), tumor size, tumor location, TNM stage, liver metastasis, chemotherapy were significantly different between MAC and AC groups. The MAC group had similar dissected lymph nodes, but more positive lymph nodes than the AC group. The overall survival (OS) of the MAC group was poorer than that of the AC group, but cancer-specific survival (CSS) was similar between the two groups. The RHC subgroup of the MAC group had more patients of age ≤60 years, larger tumor size, cecum/ascending colon location and dissected lymph nodes than the PC subgroup, but similar positive lymph nodes, perioperative mortality, OS and CSS as the PC subgroup. Moreover, the univariate and multivariable analyses for the survival of RCC patients with MAC showed that RHC might not be a superior predictor for OS and CSS compared with PC.

Conclusions: RHC could not dissect more positive lymph nodes or provide long-term survival benefits for RCC patients with MAC compared with PC. This study could provide some evidence for surgery treatment selection for MAC of RCC, which has important clinical value in individual management of colon cancer patients.

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Colorectal cancer is the third most frequently diagnosed cancer worldwide. Clinically, chemotherapeutic agents such as FOLFOX are the mainstay of colorectal cancer treatment. However, the side effects including toxicity of FOLFOX stimulated the enthusiasm for developing adjuvants, which exhibit better safety profile. Turmeric extract (TE), which has been previously shown to suppress the growth of human and murine colon xenografts, was further demonstrated here for its inhibitory effects on colon cancer patient-derived xenografts (PDX). PDX models were successfully established from tissues of colon cancer patients and the PDX preserved the heterogeneous architecture through passages. NOD/SCID mice bearing PDX were treated either with TE or FOLFOX and differential responses toward these treatments were observed. The growth of PDX, metastasis and tumor recurrence in PDX-bearing mice were suppressed after TE treatments with 60% anti-tumor response rate and 83.3% anti-metastasis rate. Mechanistic studies showed that TE reduced tumor cell proliferation, induced cell apoptosis, inhibited metastasis via modulating multiple targets, such as molecules involved in Wnt and Src pathways, EMT and EGFR-related pathways. Nevertheless, FOLFOX treatments inhibited the PDX growth with sharp decreases of mice body weight and only mild anti-metastasis activities were observed. Furthermore, in order to have a better understanding of the underlying mechanisms, network pharmacology was utilized to predict potential targets and mechanism. In conclusion, the present study demonstrated for the first time that oral TE treatment was effective to suppress the growth of colon PDX and the recurrence of colon tumors in mice. The findings obtained from this clinically relevant PDX model would certainly provide valuable information for the potential clinical use of TE in colorectal cancer patients. The application of PDX model was well illustrated here as a good platform to verify the efficacy of multi-targeted herbal extracts.

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PCRT, Preoperative chemoradiotherapy; US, Upfront surgery.
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Edited by Damiano D’Ardes, Andrea Boccatonda
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08 April 2025
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Frontiers in Cardiovascular Medicine

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Edited by Damiano D’Ardes, Andrea Boccatonda
Deadline
08 April 2025
Submit a paper