Right patient approach to experimental stromal cell therapies for gastrointestinal tumors

Abstract

Experimental therapies targeting immune and stromal cells, such as mast cells, cancer-associated fibroblasts, dendritic cells, and tumor endothelial cells, in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges. These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure, but instead reflect a true relational and cognitive process grounded in understanding, free choice, and the ability to revoke consent at any time. In particular, it is essential that the patient understands the experimental nature of the therapy, its development stage, potential benefits and risks, as well as the implications for their health and personal dignity. In the case of stromal cell-based treatments, which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood, patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes, whether beneficial or harmful, cannot yet be predicted with certainty. This requires particularly careful medical communication, using simple yet scientifically accurate explanations delivered in appropriate language, along with a final verification of the patient’s actual understanding.

Key Words: Experimental therapies; Surgery; Non-standardized treatment; Gastrointestinal tumor; Informed consent

Core Tip: Experimental therapies targeting immune stromal cells in the treatment of gastrointestinal tumors pose surgical and medico-legal challenges. Because these treatments are innovative, the patient's informed consent must reflect a genuinely relational and cognitive process grounded in understanding and free choice. It is essential that the patient understand the experimental nature of the therapy, the potential benefits and risks, as well as the implications for their health and personal dignity. Furthermore, when a patient participates in a non-standardized treatment, they must be informed that the outcomes, whether positive or negative, are not yet known with certainty.

TO THE EDITOR

The introduction of experimental therapies involving stromal immune cells such as mast cells, cancer-associated fibroblasts, dendritic cells, and tumor-associated endothelial cells into the treatment of solid gastrointestinal tumors presents new and complex challenges in both surgical and medico-legal fields[1,2]. Because these therapies are innovative, informed consent must go beyond a simple acknowledgment of the medical act. Instead, it must instead represent a meaningful relational and cognitive process, grounded in understanding, voluntary decision-making, and the patient’s right to withdraw at any time[3,4]. Patients must be clearly informed about the experimental nature of the therapy, the stage of its clinical development, the potential benefits and risks, and the implications it may have on their health and personal dignity[5,6].

In cases where stromal cell-based treatments are proposed, therapies that may induce complex immunomodulatory effects or trigger angiogenic pathways that are not yet fully understood, it is essential that patients are fully aware that they are undergoing a non-standardized, investigational treatment[7]. The possible outcomes, whether beneficial or harmful, remain uncertain. This reality demands a particularly careful approach to patient communication[8,9]. Explanations must be clear, scientifically accurate, and accessible, with particular attention to ensuring that the patient has truly understood the information presented[10].

ESSENTIAL COMPONENTS OF INFORMED CONSENT FOR STROMAL CELL-BASED EXPERIMENTAL THERAPIES

Protocols

The informed consent form must contain clear and comprehensive information, including the following elements[11] (Figure 1).

Purpose of the experimental treatment: A clear explanation of the biological rationale for the protocol, such as the use of stromal cells to inhibit or modulate tumor growth through controlled immunological or pro-angiogenic mechanisms[12].

Procedure description: A detailed outline that distinguishes among the surgical phase, adjuvant therapies, and the experimental treatment itself, specifying what the patient will undergo at each stage[13].

Foreseeable risks: Including, but not limited to, unintended stimulation of tumor angiogenesis, abnormal inflammatory responses, immunologic rejection, unpredictable systemic effects, potential therapeutic failure, and unknown long-term consequences[14].

Potential benefits: Presented only in probabilistic terms, never as guaranteed outcomes. It is important to emphasize that the treatment is still under evaluation and not yet validated[15].

Available standard therapeutic alternatives: A clear description of conventional treatment options (e.g., chemotherapy, radiation therapy, conventional surgery), including their respective efficacy rates and associated risks[16].

Biological sample storage: Information on the possible future use of collected biological samples for diagnostic or research purposes, in accordance with privacy laws and bioethical standards[17].

Insurance coverage and patient protection: Details about compensation or coverage for any harm potentially caused by the experimental treatment, as provided by applicable clinical trial regulations[18].

Right to withdraw at any time: A clear statement that the patient may withdraw from the study at any moment, without affecting access to standard care and without any form of penalty or disadvantage[19].

THE CASE OF STROMAL CELL THERAPIES IN RADICAL SURGERY FOR COLORECTAL CANCER

In the setting of operable colorectal cancer, experimental therapies involving stromal cells may be integrated as adjuvant treatment (administered after surgical resection to prevent recurrence or metastasis) or as neoadjuvant treatment (administered before surgery to reduce tumor burden and modulate the immune microenvironment)[20]. In such cases, informed consent must be provided both in written and verbal form by a physician actively involved in the clinical trial, preferably the principal investigator, and must be approved by the relevant Institutional Review Board (IRB)[17-19]. To ensure that patients fully understand the proposed treatment, the use of supplementary educational tools is strongly recommended, such as visual diagrams, explanatory videos, frequently asked questions, and simplified information sheets. The physician is also responsible for assessing the patient’s decision-making capacity and comprehension and must document every relevant informational encounter in the patient’s clinical record[3,4].

The consent form should include: (1) A modular structure with separate, clearly labeled sections for standard surgical procedures (e.g., right hemicolectomy), conventional oncologic treatments, and stromal cell-based experimental protocols[8,9,11,13]; (2) Explicit choice fields, such as “I consent / I do not consent” for each section, allowing the patient to provide selective agreement[19]; (3) A separate signature field for the authorization of biological sample use, specifying the purpose (diagnostic, therapeutic, or research)[4]; (4) A dedicated section documenting the explanations provided, as well as an invitation to ask further questions at any time, both before and during study participation[18]; (5) A statement clearly affirming that withdrawal of consent is an absolute right, which may be exercised at any moment without any negative impact on the continuity or quality of standard medical care[3]; and (6) An explicit mention of the approving IRB, including contact information for questions, concerns, or complaints regarding the study protocol[17].

CONCLUSION

In conclusion, the introduction of experimental stromal cell therapies demands renewed attention to the quality of the informed consent process[21]. It is essential that patients receive personalized, thorough, and up-to-date information not limited to paper-based documentation, but supplemented by an individualized clinical discussion. This interaction must be documented, built on trust and transparency, and tailored to the patient’s specific condition and level of understanding[4].

Figure 1 Informed consent flowchart. IRB: Institutional Review Board.

Informed consent must be seen as a dynamic process, developed over time, and not merely a formal or bureaucratic act[18,19]. From a medico-legal perspective, the adequacy of informed consent is not only a core requirement for the legitimacy of medical intervention, but also a potential ground for professional liability, especially in the context of experimental treatments[3,18,19]. The administration of a non-standardized therapy without complete and specific consent may constitute a civil, ethical, or, in more serious cases, criminal violation[4,18,19].

The integration of experimental cell-based therapies into the treatment of radically operated colorectal cancer must be grounded in a fully informed, properly documented, and ethically sound consent, in strict adherence to the principles of patient autonomy, proportionality, prudence, and justice. Such an approach bridges clinical care, scientific research, and the protection of individual dignity.