In the Journals

World Trade Center responders may face increased cancer burden, elevated myeloma risk

C. Ola Landgren, MD, PhD
C. Ola Landgren

Rescue and recovery workers who responded to the World Trade Center site after 9/11 will experience a greater cancer burden over the next 20 years than a demographically similar population, according to research published in JAMA Oncology.

The study projected incidence of prostate cancer, thyroid cancer and melanoma among New York City Fire Department (FDNY) employees who worked at the World Trade Center site will exceed typical rates in the city.

Firefighters exposed to the disaster site already have demonstrated elevated incidence of monoclonal gammopathy of undetermined significance (MGUS) — a precursor to multiple myeloma — and may be at risk for developing myeloma at an earlier age, a second study showed.

HemOnc Today spoke with researchers involved with both studies to get more insights about their findings and their potential implications.

 

Increased cancer burden

Prior research suggested elevated cancer rates among individual rescue and recovery workers exposed to the World Trade Center site compared with the general population.

Rachel Zeig-Owens, DrPH, MPH, director of epidemiology at the FDNY World Trade Center (WTC) Health Program and research assistant professor in the department of epidemiology and population health at Albert Einstein College of Medicine, and colleagues sought to project 20-year cancer incidence among FDNY rescue and recovery workers.

The analysis included 14,474 workers (mean age, 50.2 years; 96.8% male; 87.1% white) who remained alive and cancer free as of Jan. 1, 2012.

Photo of World Trade Center
Rescue and recovery workers who responded to the World Trade Center site after 9/11 will experience a greater cancer burden over the next 20 years
Source: Adobe Stock

Researchers analyzed New York City cancer rates to model age impact and FDNY WTC Health Program cancer rates to model the additional impact of carcinogen exposure.

Zeig-Owens and colleagues conducted subgroup analyses on the white male population (n = 12,374) in which they compared FDNY WTC Health Program cancer rates between 2007 and 2011 with New York City cancer rates.

Over the next 20 years, researchers projected 2,960 (95% CI, 2,883-3,037) cancer cases for the entire study cohort, 2,714 (95% CI, 2,638-2,786) cases among white men in the cohort, and 2,596 (95% CI, 2,524-2,668) cases among a demographically similar group in the general population.

Investigators projected more cases of prostate cancer (1,437 vs. 863), thyroid cancer (73 vs. 57) and melanoma (201 vs. 131) among rescue workers than the general population. However, researchers projected fewer cases of lung cancer (237 vs. 373), colorectal cancer (172 vs. 267) and kidney cancer (66 vs. 132) among rescue workers than the general population (P < .001 for all comparisons).

“This study shows all rescue/recovery workers who worked at the World Trade Center site should continue to receive cancer screening because the risk for cancer may be elevated for years to come due to their exposures,” Zeig-Owens told HemOnc Today.

After adjusting FDNY WTC Health Program rates for surveillance bias, sensitivity analysis indicated no significant difference between future case numbers of all cancers combined among white men in the FDNY WTC Health Program cohort and the general population (2,560 vs. 2,596). However, the projected number of prostate cancer cases among the rescue workers remained significantly higher than the projected number in the general population (1,271 vs. 863; P < .001).

Investigators also used claims data to determine costs of cancer care for all cancer types within the first year of diagnosis. They estimated the 20-year cost of first-year treatment within the FDNY WTC Health Program cohort would be $235,835,412 (95% CI, 187,582,227-284,088,597).

“The World Trade Center health program needs to anticipate and plan for the associated increasing costs of cancer treatment in the years that follow,” Zeig-Owens said.

 

Myeloma risk

In a separate study, C. Ola Landgren, MD, PhD, chief of myeloma service at Memorial Sloan Kettering Cancer Center, aimed to characterize World Trade Center-exposed firefighters with myeloma diagnosis, as well as conduct a screening study for MGUS and light-chain MGUS.

“To study precursor disease gives early information on the projected patterns of multiple myeloma in the future,” Landgren told HemOnc Today.

Prior research has shown increased risk for multiple myeloma and precursor conditions among individuals exposed to various carcinogens, including polychlorinated biphenyl, polycyclic aromatic hydrocarbons, dioxins and asbestos.

One study of 55,778 residents in New York state enrolled in the World Trade Center Health Registry showed a nearly threefold higher risk for multiple myeloma (standardized incidence ratio = 2.85; 95% CI, 1.15-5.88) based on seven cases. After long-term follow-up to determine cancer incidence patterns, researchers found the same World Trade Center cohort had only a 1.4-fold increased risk for multiple myeloma.

“At Memorial Sloan Kettering Cancer Center, over the past few years, we have seen several newly diagnosed multiple myeloma cases diagnosed among World Trade Center-exposed firefighters and rescue workers,” Landgren said. “Many have been younger and also had a more rapid disease trajectory compared with what we are used to seeing. Our clinical inclination has been that there is something going on, and we were prompted to reach out to FDNY to design a collaborative study on this topic.”

Landgren and colleagues identified 12,942 firefighters from FDNY exposed to toxins at the World Trade Center site. Of these, 16 were diagnosed with multiple myeloma (median age at diagnosis, 57 years) between September 12, 2001, and July 1, 2017. Researchers used these incidences as a case series population in the analysis.

Investigators also conducted a screening study for myeloma precursor disease. They analyzed serum samples from 1,173 exposed firefighters collected during routine monitoring examinations provided by the FDNY WTC Health Program between December 2013 and October 2015.

The final study cohort included 781 white male firefighters whose serum was tested for MGUS and light-chain MGUS.

Researchers reviewed the firefighters’ serum results along with a comparison population of 7,612 white men (age range, 50 to 79 years) from the population-based Olmsted County, Minnesota, study, the only available screening study with MGUS and light-chain MGUS assays.

Overall prevalence of MGUS among the Olmsted County population was 4.4% (n = 333).

Among the 16 firefighters with multiple myeloma, the median time between the World Trade Center attacks and diagnosis was 12 years (range, 1-15.7).

Fourteen firefighters had available serum/urine monoclonal protein isotype and free light-chain data. Of these, seven (50%) had light-chain multiple myeloma.

Review of myeloma cells for CD20 expression in a subset of seven patients determined five had CD20 expression (71%).

Researchers assayed peripheral blood from the 781 firefighters. They determined an age-standardized prevalence rate of 7.63 per 100 persons for MGUS and light-chain MGUS combined (95% CI, 5.45-9.81), compared with 4.34 per 100 persons in the Olmsted County cohort (95% CI, 3.88-4.81).

The prevalence among the firefighters was 1.8-fold higher than that of the Olmsted County population (relative rate [RR] = 1.76; 95% CI, 1.34-2.29).

Firefighters demonstrated a threefold higher age-standardized prevalence rate of light-chain MGUS than the Olmsted County population (RR = 3.13; 95% CI, 1.99-4.93).

“Our study shows that there is a doubling in the prevalence of myeloma precursor disease among World Trade Center-exposed firefighters compared with the general population,” Landgren said. “When we characterized all World Trade Center-exposed firefighters with newly diagnosed multiple myeloma compared with the general population, we found 10 to 15 years earlier age of onset for multiple myeloma. Also, we found markers of more aggressive myeloma biology to be more common among these patients.”

 

Potential of overdiagnosis

Otis Brawley
Otis W. Brawley

Cancers are often associated with environmental exposures, Otis W. Brawley, MD, MACP, chief medical officer at American Cancer Society and a HemOnc Today Editorial Board member, wrote in an editorial that accompanied these two studies in JAMA Oncology.

“When these World Trade Center heroes are diagnosed as having a cancer, even a cancer common in the population, there is a natural tendency to assume it is due to their service at the World Trade Center,” Brawley wrote.

Landgren and colleagues identified an association between workers and multiple myeloma; however, the number of myeloma cases was small.

“It is difficult to make a firm correlation with World Trade Center service,” Brawley wrote. “There may be a latency period, and, over time, this group may have a larger number of patients with myeloma, and a link to World Trade Center exposure may become more apparent.”

Brawley also noted a potential for biased screening, indicating that the firefighters could have been screened for MGUS more aggressively than the Olmsted County cohort.

“A general rule of screening is increased surveillance leads to increased disease incidence,” Brawley said. “Overdiagnosis is a bias of screening.”

The data suggested screening for MGUS appeared associated with overdiagnosis, he added.

In the study by Singh and colleagues, prostate cancer, thyroid cancer and melanoma increased over time among rescue workers.

Increased incidence and mortality from these cancers has been reported in previous studies with firefighters from other cities, Brawley noted.

“Are the predicted increases due to World Trade Center exposure or a career as a firefighter? These are also cancers associated with overdiagnosis,” Brawley said.

Regimented screening for prostate and thyroid cancers leads to more diagnoses, he noted.

“Landgren and colleagues note that they cannot find an exposure gradient,” Brawley wrote. “They report that the World Trade Center exposure may be a risk factor for the development of multiple myeloma and its precursor disease, MGUS. This is appropriately worded. The operative word is ‘may.’

“These trials, because of the size of the cohort, cannot identify a small increase in cancer risk due to World Trade Center exposure, and correlation does not mean causation,” he added. ““Perhaps this issue is beyond the limits of science.” – by Melinda Stevens

 

For more information:

C. Ola Landgren, MD, PhD, can be reached at landgrec@mskcc.org.

Rachel Zeig-Owens, DrPH, can be reached at rachel.zeig-owens@fdny.nyc.gov.

 

Disclosures: The study authors and Brawley report no relevant financial disclosures.

C. Ola Landgren, MD, PhD
C. Ola Landgren

Rescue and recovery workers who responded to the World Trade Center site after 9/11 will experience a greater cancer burden over the next 20 years than a demographically similar population, according to research published in JAMA Oncology.

The study projected incidence of prostate cancer, thyroid cancer and melanoma among New York City Fire Department (FDNY) employees who worked at the World Trade Center site will exceed typical rates in the city.

Firefighters exposed to the disaster site already have demonstrated elevated incidence of monoclonal gammopathy of undetermined significance (MGUS) — a precursor to multiple myeloma — and may be at risk for developing myeloma at an earlier age, a second study showed.

HemOnc Today spoke with researchers involved with both studies to get more insights about their findings and their potential implications.

 

Increased cancer burden

Prior research suggested elevated cancer rates among individual rescue and recovery workers exposed to the World Trade Center site compared with the general population.

Rachel Zeig-Owens, DrPH, MPH, director of epidemiology at the FDNY World Trade Center (WTC) Health Program and research assistant professor in the department of epidemiology and population health at Albert Einstein College of Medicine, and colleagues sought to project 20-year cancer incidence among FDNY rescue and recovery workers.

The analysis included 14,474 workers (mean age, 50.2 years; 96.8% male; 87.1% white) who remained alive and cancer free as of Jan. 1, 2012.

Photo of World Trade Center
Rescue and recovery workers who responded to the World Trade Center site after 9/11 will experience a greater cancer burden over the next 20 years
Source: Adobe Stock

Researchers analyzed New York City cancer rates to model age impact and FDNY WTC Health Program cancer rates to model the additional impact of carcinogen exposure.

Zeig-Owens and colleagues conducted subgroup analyses on the white male population (n = 12,374) in which they compared FDNY WTC Health Program cancer rates between 2007 and 2011 with New York City cancer rates.

Over the next 20 years, researchers projected 2,960 (95% CI, 2,883-3,037) cancer cases for the entire study cohort, 2,714 (95% CI, 2,638-2,786) cases among white men in the cohort, and 2,596 (95% CI, 2,524-2,668) cases among a demographically similar group in the general population.

Investigators projected more cases of prostate cancer (1,437 vs. 863), thyroid cancer (73 vs. 57) and melanoma (201 vs. 131) among rescue workers than the general population. However, researchers projected fewer cases of lung cancer (237 vs. 373), colorectal cancer (172 vs. 267) and kidney cancer (66 vs. 132) among rescue workers than the general population (P < .001 for all comparisons).

“This study shows all rescue/recovery workers who worked at the World Trade Center site should continue to receive cancer screening because the risk for cancer may be elevated for years to come due to their exposures,” Zeig-Owens told HemOnc Today.

After adjusting FDNY WTC Health Program rates for surveillance bias, sensitivity analysis indicated no significant difference between future case numbers of all cancers combined among white men in the FDNY WTC Health Program cohort and the general population (2,560 vs. 2,596). However, the projected number of prostate cancer cases among the rescue workers remained significantly higher than the projected number in the general population (1,271 vs. 863; P < .001).

Investigators also used claims data to determine costs of cancer care for all cancer types within the first year of diagnosis. They estimated the 20-year cost of first-year treatment within the FDNY WTC Health Program cohort would be $235,835,412 (95% CI, 187,582,227-284,088,597).

“The World Trade Center health program needs to anticipate and plan for the associated increasing costs of cancer treatment in the years that follow,” Zeig-Owens said.

 

Myeloma risk

In a separate study, C. Ola Landgren, MD, PhD, chief of myeloma service at Memorial Sloan Kettering Cancer Center, aimed to characterize World Trade Center-exposed firefighters with myeloma diagnosis, as well as conduct a screening study for MGUS and light-chain MGUS.

“To study precursor disease gives early information on the projected patterns of multiple myeloma in the future,” Landgren told HemOnc Today.

Prior research has shown increased risk for multiple myeloma and precursor conditions among individuals exposed to various carcinogens, including polychlorinated biphenyl, polycyclic aromatic hydrocarbons, dioxins and asbestos.

One study of 55,778 residents in New York state enrolled in the World Trade Center Health Registry showed a nearly threefold higher risk for multiple myeloma (standardized incidence ratio = 2.85; 95% CI, 1.15-5.88) based on seven cases. After long-term follow-up to determine cancer incidence patterns, researchers found the same World Trade Center cohort had only a 1.4-fold increased risk for multiple myeloma.

“At Memorial Sloan Kettering Cancer Center, over the past few years, we have seen several newly diagnosed multiple myeloma cases diagnosed among World Trade Center-exposed firefighters and rescue workers,” Landgren said. “Many have been younger and also had a more rapid disease trajectory compared with what we are used to seeing. Our clinical inclination has been that there is something going on, and we were prompted to reach out to FDNY to design a collaborative study on this topic.”

Landgren and colleagues identified 12,942 firefighters from FDNY exposed to toxins at the World Trade Center site. Of these, 16 were diagnosed with multiple myeloma (median age at diagnosis, 57 years) between September 12, 2001, and July 1, 2017. Researchers used these incidences as a case series population in the analysis.

Investigators also conducted a screening study for myeloma precursor disease. They analyzed serum samples from 1,173 exposed firefighters collected during routine monitoring examinations provided by the FDNY WTC Health Program between December 2013 and October 2015.

The final study cohort included 781 white male firefighters whose serum was tested for MGUS and light-chain MGUS.

Researchers reviewed the firefighters’ serum results along with a comparison population of 7,612 white men (age range, 50 to 79 years) from the population-based Olmsted County, Minnesota, study, the only available screening study with MGUS and light-chain MGUS assays.

Overall prevalence of MGUS among the Olmsted County population was 4.4% (n = 333).

Among the 16 firefighters with multiple myeloma, the median time between the World Trade Center attacks and diagnosis was 12 years (range, 1-15.7).

Fourteen firefighters had available serum/urine monoclonal protein isotype and free light-chain data. Of these, seven (50%) had light-chain multiple myeloma.

Review of myeloma cells for CD20 expression in a subset of seven patients determined five had CD20 expression (71%).

Researchers assayed peripheral blood from the 781 firefighters. They determined an age-standardized prevalence rate of 7.63 per 100 persons for MGUS and light-chain MGUS combined (95% CI, 5.45-9.81), compared with 4.34 per 100 persons in the Olmsted County cohort (95% CI, 3.88-4.81).

The prevalence among the firefighters was 1.8-fold higher than that of the Olmsted County population (relative rate [RR] = 1.76; 95% CI, 1.34-2.29).

Firefighters demonstrated a threefold higher age-standardized prevalence rate of light-chain MGUS than the Olmsted County population (RR = 3.13; 95% CI, 1.99-4.93).

“Our study shows that there is a doubling in the prevalence of myeloma precursor disease among World Trade Center-exposed firefighters compared with the general population,” Landgren said. “When we characterized all World Trade Center-exposed firefighters with newly diagnosed multiple myeloma compared with the general population, we found 10 to 15 years earlier age of onset for multiple myeloma. Also, we found markers of more aggressive myeloma biology to be more common among these patients.”

 

Potential of overdiagnosis

Otis Brawley
Otis W. Brawley

Cancers are often associated with environmental exposures, Otis W. Brawley, MD, MACP, chief medical officer at American Cancer Society and a HemOnc Today Editorial Board member, wrote in an editorial that accompanied these two studies in JAMA Oncology.

“When these World Trade Center heroes are diagnosed as having a cancer, even a cancer common in the population, there is a natural tendency to assume it is due to their service at the World Trade Center,” Brawley wrote.

Landgren and colleagues identified an association between workers and multiple myeloma; however, the number of myeloma cases was small.

“It is difficult to make a firm correlation with World Trade Center service,” Brawley wrote. “There may be a latency period, and, over time, this group may have a larger number of patients with myeloma, and a link to World Trade Center exposure may become more apparent.”

Brawley also noted a potential for biased screening, indicating that the firefighters could have been screened for MGUS more aggressively than the Olmsted County cohort.

“A general rule of screening is increased surveillance leads to increased disease incidence,” Brawley said. “Overdiagnosis is a bias of screening.”

The data suggested screening for MGUS appeared associated with overdiagnosis, he added.

In the study by Singh and colleagues, prostate cancer, thyroid cancer and melanoma increased over time among rescue workers.

Increased incidence and mortality from these cancers has been reported in previous studies with firefighters from other cities, Brawley noted.

“Are the predicted increases due to World Trade Center exposure or a career as a firefighter? These are also cancers associated with overdiagnosis,” Brawley said.

Regimented screening for prostate and thyroid cancers leads to more diagnoses, he noted.

“Landgren and colleagues note that they cannot find an exposure gradient,” Brawley wrote. “They report that the World Trade Center exposure may be a risk factor for the development of multiple myeloma and its precursor disease, MGUS. This is appropriately worded. The operative word is ‘may.’

“These trials, because of the size of the cohort, cannot identify a small increase in cancer risk due to World Trade Center exposure, and correlation does not mean causation,” he added. ““Perhaps this issue is beyond the limits of science.” – by Melinda Stevens

 

For more information:

C. Ola Landgren, MD, PhD, can be reached at landgrec@mskcc.org.

Rachel Zeig-Owens, DrPH, can be reached at rachel.zeig-owens@fdny.nyc.gov.

 

Disclosures: The study authors and Brawley report no relevant financial disclosures.