Factors influencing clinical response to neoadjuvant therapy among patients with wilms tumor at Muhimbili national hospital.

Abstract

ABSTRACT Background: The combination of neo-adjuvant therapy, surgery, and adjuvant therapy has resulted in a cure rate exceeding 90% for non-metastatic Wilms' tumors in developed nations, yet the cure rate in low-income countries is inferior. Neo-adjuvant therapy is essential for reducing tumor size, down-staging the disease, and enhancing surgical outcomes. Nonetheless, despite the completion of neo-adjuvant therapy, available evidence in our setting reveals a proportion of patients presenting with gross tumors intraoperatively. This increases the likelihood of tumor rupture and spillage, impacting the overall treatment outcomes of Wilms tumor patients. Aim: The primary objective of this study was to determine the factors influencing clinical responses to neo-adjuvant therapy among patients with Wilms tumors at Muhimbili National Hospital (MNH) in Dar es Salaam. Methods: A retrospective hospital-based cross-sectional analytical study was conducted at Muhimbili National Hospital in Dar es Salaam, enrolling data from children diagnosed with Wilms tumors between January 1, 2018 and December 31, 2023. Data on patients' demographics, nutritional status, site of the disease, stage of the disease, histological subtype, treatment regime, and intraoperative complications (such as tumor rupture or spillage) were collected. We analyzed the data using SPSS version 26. The prevalence ratio was used as a measure of association between dependent and independent variables, with a p-value of less than 0.05 considered statistically significant. Results: A total of 113 Wilms tumor patients who met the inclusion criteria were recruited in the study; 69.1% (n = 70) were aged four years or younger, and the rest (38.9%) were older than 4 years (n = 43). The median age at presentation was 48 months, with an interquartile range (IQR) of 24 to 60 months and an approximate male to-female ratio of 1:1. The right and left kidneys were affected equally and synchronous bilateral disease found in only one patient. Abdominal mass or swelling was a predominant symptom (98.2%), with 46% presenting with stages III and IV (advanced vi disease) at the time of diagnosis. The majority of the patients had an intermediate-risk histology (63.7%), a low-risk 7.1%, and a high-risk 29.2%. The overall response to neoadjuvant chemotherapy in tumor volume reduction among patients with Wilms tumors in our setting is significant (P<0.001); however, its effect is hindered by delayed presentation with advanced disease, an older age group, and malnutrition presenting with relatively large tumor volume at the time of diagnosis (P<0.05). About 42.5% experienced a major decrease in tumor volume (> 50%), and the majority of the patients exhibited a stable disease (63.7%), (29.2%) a partial response, and 6.2% experienced a progressive disease. Tumor spillage was the predominant intraoperative complication (23%), and it was significantly associated with the older age group. Conclusion: Late presentation with older age group, advanced disease and malnutrition at diagnosis are modifiable essential factors to enhance the neoadjuvant therapy clinical response among Wilms tumor patients at MNH. This will reduce intraoperative tumor rupture and spillage and improve the overall treatment outcomes. Keywords; Neoadjuvant therapy, Wilms tumor,