Hemostatic radiotherapy for bleeding gastrointestinal tumors

Abstract

Hemostatic radiotherapy is a non-invasive treatment for bleeding gastrointestinal (GI) tumors, promoting tumor shrinkage, blood supply reduction, and fibrotic tissue formation. It is effective in cases where traditional interventions are insufficient or contraindicated and can prevent recurrent bleeding in patients with GI bleeding histories. Hypofractionation schedules are also effective for tumor control and patient compliance.

Core Tip: Hemostatic radiotherapy (RT), a non-invasive approach, is used in bleeding gastrointestinal (GI) tumors to induce tumor shrinkage and diminish blood supply. This therapy reduces tumor size, seals ruptured blood vessels and reduces bleeding. It also fosters fibrotic tissue formation and enhances platelet adhesion to the vascular endothelium. Hemostatic RT is particularly relevant when traditional interventions are insufficient or contraindicated, and can prevent recurrent bleeding in patients with a history of GI bleeding tumors. The optimal dose fractionation for hemostatic RT is debated, but hypofractionation schedules have proven effective for tumor control and patient compliance.

TO THE EDITOR

We have had the opportunity to study the research conducted by Pan et al[1], which delves into the effectiveness and safety of gastroscopic hemostasis in the management of acute gastric hemorrhage. The meta-analysis provides a detailed account of the methodologies and outcomes, encompassing multiple randomized controlled trials comparing endoscopic hemostasis with control interventions. The findings indicate that endoscopic hemostasis surpasses the control group in hemostasis rate, with lower rebleeding and surgical transfer rates, reduced serum levels of inflammatory factors, and an elevated rate of improvement in the quality of life.

Gastrointestinal (GI) tumors, including malignancies such as gastric cancer, colorectal cancer, and GI stromal tumors (GISTs), may present with life-threatening bleeding complications[2]. The altered architecture of tumor vessels, particularly in the smooth muscle layer, poses challenges for conventional interventions like endoscopic hemostasis, surgical resection, and embolization. Hemostatic RT emerges as an alternative strategy, employing targeted ionizing radiation to induce tumor shrinkage and diminish blood supply.

Hemostatic radiotherapy (RT) leverages the principles of ionizing radiation to elicit biological effects within the tumor tissue. High-energy photons or particles penetrate the tumor, causing DNA damage and cellular death. In the context of bleeding GI tumors, this approach seeks hemostasis through tumor shrinkage, vascular alterations, or fibrosis. The induced cellular damage reduces tumor size, potentially sealing ruptured blood vessels and mitigating bleeding, while also inducing changes in the tumor vasculature, leading to decreased blood supply and, consequently, reduced bleeding. RT fosters the formation of fibrotic tissue, aiding in the closure of vascular defects and stabilizing the tumor microenvironment. Additionally, radiation is believed to induce a prothrombotic state and enhance platelet adhesion to the vascular endothelium[3-5].

Hemostatic RT is especially relevant when traditional interventions are contraindicated or insufficient. It serves as a non-invasive alternative when surgical resection is challenging due to tumor location or extent, or when patients are unfit for intervention. Individuals at high risk for surgery, owing to comorbidities or advanced age, may benefit from the hemostatic effects of RT. As an adjuvant treatment, hemostatic RT can prevent recurrent bleeding in patients with a history of GI bleeding tumors. In cases where the primary objective is symptom control and quality of life improvement, hemostatic RT can be applied in a palliative context.

The evidence supporting hemostatic RT in bleeding GI tumors is evolving, with clinical studies and case reports demonstrating its efficacy in achieving hemostasis and improving patient outcomes[5-8]. The optimal dose fractionation remains a subject of debate, with high doses per fraction commonly employed for hemostatic purposes. Hypofractionation schedules, dividing the total radiation dose into a few large doses, have proven effective for tumor control and patient compliance[9]. The ideal fractionation regimen for hemostatic RT is undetermined, with bleeding typically ceasing after a biologically effective dose of 20 Gy has been delivered. Doses commonly used include 8 Gy in a single fraction, 12 Gy over 3 fractions, 15 Gy over 5 fractions, 20 Gy over 5 fractions, or 30 Gy in 10 fractions. Bleeding in urinary bladder cancers, head and neck cancers, gynecological malignancies and skin lesions have also been shown to be controlled using RT using various dose fractionation regimens including the ones stated previously[10].

Hemostatic RT does have toxicities albeit they are mostly grade 1 and 2. Toxicities included nausea, thrombocytopenia, neutropenia, diarrhea, and deranged liver enzymes. In addition, hemostatic RT takes between 1-9 d (median 2 d) to act, unlike other interventions that are almost immediate in their action. Approximately 73% of patients benefit from hemostatic RT[8].

In our institution, we treated nine patients in the past year, either exclusively for hemostasis (four patients) or with hemostasis as a concurrent goal in palliative care (five patients). Among these, five patients had locally advanced or metastatic GI malignancies. Treatment with 30 Gy in 10 fractions and 8 Gy in a single fraction yielded equivalent results, with hemostasis generally occurring around 24 h after the 8 Gy regimen and after 3-4 fractions with the 30 Gy regimen in GI malignancies, without acute toxicities. Two recorded mortalities were unrelated to bleeding issues (cancer progression without bleeding).

In conclusion, while gastroscopic hemostasis and embolization play important roles, hemostatic RT emerges as a promising therapeutic modality for achieving hemostasis in bleeding GI tumors. The ongoing evolution of this field holds the potential to augment the clinical toolkit, empowering clinicians in their endeavors to enhance patient outcomes in the face of bleeding GI tumors.