Trends in mortality from secondary malignancy in the United States, 1999-2019.
Authors: Farhan Syed Ali , Farhan Syed Husain , Nasir Muhammad Moiz , Mahmood Umar , Haris Muhammad , Laique Fatima , Mukhtar Sameen , Ahmed Jawad , Siddiqi Rabbia , Iqbal Abdul Ghani , Memon Roha Saeed , Waqar Syed Hamza Bin 
Published: June 2024

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Background: Recent advancements in cancer diagnosis, treatment, and supportive care increased the survivorship of cancer patients. However, the risk of secondary malignancy (SM), associated most commonly with side effects of radiation and chemotherapies, has emerged as a looming threat to childhood and adult-onset cancer survivors. Recognizing the recent trends in malignancy-related deaths and the risk factors associated could assist healthcare professionals and policymakers in constructing appropriate guidelines for timely diagnosis and individual patient-dependent treatment regimens. Hence, our CDC analysis focuses on highlighting trends in mortality from SM from “1999 to 2019”. Methods: Using the deidentified death certificate data from the CDC WONDER database, we analyzed mortality trends from 1999 to 2019 for SM. Age-adjusted mortality rates (AAMRs) per 100,000 people were calculated for the total population, stratified by gender, race, age, and site of SM. Annual percent change (APC) was calculated using the Joinpoint regression software. Results: A total of 1,499,108 deaths occurred from 1999 to 2019 in the US. The overall AAMR showed a decrease from 27.5 in 1999 to 18.83 in 2007 (APC: -4.71), remained at a relatively constant level of 19.11 till 2013 (APC: 0.48), followed by a rapid rise to 23.29 in 2017 (APC: 5.37), and finally a gradual rise to 24.29 in 2019 (APC: 1.97). Men showed consistently higher AAMR than women throughout the study period between 1999 (AAMR Men: 33.31 vs Women: 23.78) and 2019 (AAMR Men: 28.03 vs Women: 21.51). Moreover, Black (AAMR: 23.89) showed the highest mortality rate, followed by Whites (AAMR: 21.46). American Indian (AAMR: 13.93), Asian (AAMR: 13.89), and Hispanic (AAMR: 15.9) showing similar mortality trends. Furthermore, AAMR increased with age, showing the highest mortality rates in patients 75+ yrs (148.3), followed by 55-74 yrs (61.6), 35-54 yrs (9.23), 15-34 yrs (0.7), and ≤ 14 yrs (0.19). More recently the greatest rise in SM from 2013-2019 was observed in adrenal glands (APC: 11.8), bone and bone marrow (APC: 8.7), kidney and renal pelvis (APC: 7.6), and small intestine (APC: 6.9). Less prominent rise was seen in all other types of SM. Conclusions: Despite recent advances in cancer treatments, SM remains one of the most common causes of death in cancer survivors. Our analysis shows that age, gender, race, and site are important factors influencing the risk of SM-related mortality. Although the risk of SM varies across the spectrum of age, findings from one age group could be translated into preventive and screening strategies across other age groups. Guidelines for survivors should be taken into account based on prior treated malignancy and the risk of future ones. Large population based studies are imperative to understand factors behind the recent rise in SM-related mortalities from 2013 onwards.