Chronic Liver Disease and Radiation-induced Second Primary Liver Malignancy

Chronic Liver Disease and Radiation-induced Second Primary Liver Malignancy: a SEER Database Analysis 2010-2021

Cancer survivors are at a high risk to develop second primary malignancy (SPM) which constitutes a serious threat for them. Radiotherapy is the cornerstone for the management of many cancers as a locoregional treatment modality. Due to the low liver tolerance, cirrhotic patients are at a high risk of developing radiation-induced liver toxicities despite the modern safe radiation delivery techniques. Radiation damages cells through direct energy deposition and reactive free radical generation. Recent studies demonstrated a potential risk of SPMs following radiotherapy with further investigations for strategies to decrease radiation-induced SPMs. However, it is insufficiently addressed if developing liver SPMs is a serious adverse event following radiotherapy for cirrhotic patients. The aim of this study was to quantitatively assess the risk of gastrointestinal (GI) and liver SPMs following radiotherapy in patients with chronic liver disease.

Study Overview

• Status: Completed
• Conditions: Cancer; Liver Fibrosis; Chronic Liver Disease (CLD)
• Intervention / Treatment: Radiation: radiotherapy; Other: No intervention

Detailed Description

The SEER.stat software version 8.4.3 was used to obtain and analyze the data of patients with chronic liver disease diagnosed from 2010 to 2021. Using Ishak fibrosis score: F0-4 no to moderate fibrosis and F5-6 advanced or severe cirrhosis. patients were subgrouped according to the history of receiving radiotherapy for prior cancer treatment in two groups and excluded patients with unknown radiotherapy administration history. An MP-SIR session was used to calculate the Standardized Incidence Ratio (SIR) as Observed/Expected (O/E) with 95% confidence interval (CI). Significance was achieved at 0.05.

• Study Type: Observational
• Enrollment (Actual): 20846

Contacts and Locations

Study Locations

• Egypt
  • Ismailia, Egypt
    • Suez Canal University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Using the Surveillance, Epidemiology and End Results (SEER) database (17 Registries, 2000-2021, November 2023 Submission), maintained by the National Cancer Institute (NCI) containing a population-based cancer incidence and survival data from 17 registries covering approximately 28% of the U.S. population to extract the data of cancer patients with chronic liver disease diagnosed from 2010 to 2021. Patients were classified according to fibrosis severity using the Ishak fibrosis score: F0-F4 (no to moderate fibrosis) and F5-F6 (advanced or severe cirrhosis) from 2010 to 2021. Patients were stratified based on previous radiotherapy exposure into two groups; who received radiotherapy including beam radiation, radioactive implants, radioisotopes, combinations, or unspecified radiotherapy methods and patients who received no radiotherapy.

Description

Inclusion Criteria:

• Cancer patients were classified according to fibrosis severity using the Ishak fibrosis score: F0-F4 (no to moderate fibrosis) and F5-F6 (advanced or severe cirrhosis) from 2010 to 2021.

Exclusion Criteria:

• Patients with unknown radiotherapy history or unknown fibrosis score or missing age data

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with no to moderated liver fibrosis (ISHAK 0-4); They were subgrouped according to previous history of radiotherapy exposure into two groups. Both groups were followed up for 10 years to assess the risk of second primary malignancies. The investigators retrospectively analyzed the data.	Radiation: radiotherapy; The impact of previous radiotherapy exposure was studied on developing second primary malignancies.; Other: No intervention; This group received no radiotherapy
Patients with advanced or severe liver fibrosis (ISHAK 5-6); They were subgrouped according to previous history of radiotherapy exposure into two groups. Both groups were followed up for 10 years to assess the risk of second primary malignancies. The investigators retrospectively analyzed the data.	Radiation: radiotherapy; The impact of previous radiotherapy exposure was studied on developing second primary malignancies.; Other: No intervention; This group received no radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The standardized incidence ratio and excess risk of developing gastrointestinal and liver second primary malignancies following radiotherapy exposure in patients with chronic liver disease (ISHAK 0-4)	The surveillance, epidemiology and End Results (SEER) database was used to calculate the standardized incidence ratio (SIR) as Observed/Expected (O/E) and calculated the Excess absolute risk for multiple primary gastrointestinal and liver malignancies following radiotherapy exposure in patients with chronic liver disease (ISHAK 0-4)	from Jan, 2010 till Dec, 2021
The standardized incidence ratio and excess risk of developing gastrointestinal and liver second primary malignancies following radiotherapy exposure in patients with chronic liver disease (ISHAK 5-6)	The surveillance, epidemiology and End Results (SEER) database was used to calculate the standardized incidence ratio (SIR) as Observed/Expected (O/E) and calculated the Excess absolute risk for multiple primary gastrointestinal and liver malignancies following radiotherapy exposure in patients with chronic liver disease (ISHAK 5-6)	from Jan, 2010 till Dec, 2021

Collaborators and Investigators

• Sponsor: Suez Canal University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2010
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): December 30, 2021

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 6, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Liver fibrosis; SEER; chronic liver; ISHAK score
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Fibrosis; Liver Diseases; Liver Cirrhosis
• Other Study ID Numbers: H2730

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No