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A third person living with HIV has been cured by transplant
In a first, If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.
“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.
The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.
But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.
The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.
In this case, the physicians treating her used both.
“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.
Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.
One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.
This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.
“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”
The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.
“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.
“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.
And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”
Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.
But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.
For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.
“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”
Now the challenge is to move from a single case to making cure available to other people living with HIV.
The case also got cure researchers thinking.
Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.
Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”
For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.
“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”
Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.
“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”
When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.
“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”
The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a first, If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.
“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.
The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.
But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.
The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.
In this case, the physicians treating her used both.
“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.
Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.
One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.
This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.
“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”
The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.
“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.
“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.
And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”
Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.
But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.
For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.
“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”
Now the challenge is to move from a single case to making cure available to other people living with HIV.
The case also got cure researchers thinking.
Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.
Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”
For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.
“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”
Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.
“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”
When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.
“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”
The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a first, If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.
“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.
The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.
But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.
The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.
In this case, the physicians treating her used both.
“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.
Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.
One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.
This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.
“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”
The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.
“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.
“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.
And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”
Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.
But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.
For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.
“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”
Now the challenge is to move from a single case to making cure available to other people living with HIV.
The case also got cure researchers thinking.
Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.
Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”
For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.
“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”
Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.
“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”
When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.
“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”
The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CROI 2022
Eighteen-year study shows inconsistencies in treating, classifying JIA
“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.
Long-term management of JIA
In an accompanying editorial, Jaime Guzman, MD, MSc, and Ross E. Petty, MD, PhD, of British Columbia Children’s Hospital and the University of British Columbia, Vancouver, said a rheumatologist’s interpretation of the study would be tied to what they learned about children with arthritis in medical school. They would see the glass as “half full” if children who achieved remission stayed in remission if they learned that a child might end up outgrowing JIA but potentially develop lifelong disability, whereas others may focus on the outcome of approximately half of patients not achieving remission.
“When I was going through medical school, I remember learning that JIA is a disease of children, and typically, they outgrow it as they become adults,” Dr. Hausmann said. “I think this study and many other studies have shown that that’s actually not the case – that, in fact, it may be a majority of kids continue having active disease even through adulthood.”
If a rheumatologist knows JIA is likely to continue into adulthood, “that’s huge,” Dr. Hausmann said. “That means when we first diagnose patients with JIA as kids, we need to set expectations with the families that this may not just go away; this may be something that could be more lifelong.”
Education on the part of the patient, their parents, and their clinician on the expected trajectory of the disease is critical so that children can continue their own care as they transition to adulthood, Dr. Hausmann explained. “The earlier the kids develop the skills to discuss their medicines, their side effects, the better they’ll be able to transition to adult medicine,” he said.
For the patients who go into remission and stay in remission, the message is also important. “To have the reassurance that a lot of those kids won’t be having active joint symptoms or need to be on medication, that’s a huge positive message that can get out there, so I think that’s great,” Dr. Imundo said.
Time to move on from ILAR classification?
Another big takeaway from the study was how patients’ ILAR classification changed across the 18-year follow-up. First proposed in 1995, the JIA ILAR classification has been revised several times for clarification purposes. In its current form, the ILAR classification considers a patient’s history when categorizing JIA types but also includes factors such as immediate family history. This system of assessing JIA has been criticized and there are initiatives to create a new JIA classification system to replace it.
“The ILAR criteria were designed to classify patients 6 months after disease onset in an attempt to find some commonality in clinical phenotypes, prognosis, and suggested management,” Dr. Wahezi said. “While there continues to be debate as to whether we can improve our classification of JIA patients, it is not surprising that phenotypes may evolve over time as new clinical features develop. As pediatric rheumatologists, we are well accustomed to having to modify management plans as children manifest with new clinical features over time.”
Although the percentage of patients who switched ILAR classifications over the study period was “much higher” than she would have thought, Dr. Imundo said it was the reasons provided in the study that seemed odd to her. “The classification scheme relies on your family history, like someone else in your family now has psoriasis, so your arthritis classification changes,” she explained.
“We want to head toward a much more unified classification scheme, a simpler one. We now understand that some of the diseases that we see in pediatrics are really the equivalent or same disease in adults,” she said.
“Most of the pediatric categories of JIA have distinct adult correlates,” Dr. Hausmann agreed. RF-positive polyarthritis in children and rheumatoid arthritis in adults are correlated, as are systemic JIA and adult-onset Still’s disease, he explained. “That has been borne out also by genetic susceptibility studies that the genetic predispositions to systemic arthritis in children is the same as the genetic predisposition to adult-onset Still’s disease in adults. By and large, there are a lot of similarities between the two.
“I think we need to incorporate some of that knowledge in better classifying kids with JIA so that we can find the best treatments and the best outcomes, and we can provide information to families about the expected course of the disease over time so that can inform our discussions.”
Some pediatric rheumatologists accept the classification system is flawed, but not all concur with the degree to which these problems impact patient care. “While the ILAR classification criteria may be subject to criticism, it does provide general context and prognostic implications for patients and families,” Dr. Wahezi said.
“The medicines certainly are very similar across the JIA categories, so the implications are not as broad” when classification changes,” Dr. Hausmann said. “But it certainly shows that there are things that we still don’t know. I think classification is actually pretty important because it might give you a sense of how persistent the disease will be.”
Dr. Imundo said the ILAR classification’s “time is limited,” and rheumatologists may soon need to adopt a new way of classifying children with rheumatic disease – “a more data-driven, genetics-driven scheme.”
“These categories are so imperfect, and the patients are changing. I feel like that says to me, let’s find something that’s more predictive that really helps us a little better than what we have now,” she said.
The study had no specific funding. The authors of the study and the editorial have disclosed no relevant financial relationships. Dr. Hausmann reports receiving salary support from CARRA. Dr. Imundo and Dr. Wahezi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.
Long-term management of JIA
In an accompanying editorial, Jaime Guzman, MD, MSc, and Ross E. Petty, MD, PhD, of British Columbia Children’s Hospital and the University of British Columbia, Vancouver, said a rheumatologist’s interpretation of the study would be tied to what they learned about children with arthritis in medical school. They would see the glass as “half full” if children who achieved remission stayed in remission if they learned that a child might end up outgrowing JIA but potentially develop lifelong disability, whereas others may focus on the outcome of approximately half of patients not achieving remission.
“When I was going through medical school, I remember learning that JIA is a disease of children, and typically, they outgrow it as they become adults,” Dr. Hausmann said. “I think this study and many other studies have shown that that’s actually not the case – that, in fact, it may be a majority of kids continue having active disease even through adulthood.”
If a rheumatologist knows JIA is likely to continue into adulthood, “that’s huge,” Dr. Hausmann said. “That means when we first diagnose patients with JIA as kids, we need to set expectations with the families that this may not just go away; this may be something that could be more lifelong.”
Education on the part of the patient, their parents, and their clinician on the expected trajectory of the disease is critical so that children can continue their own care as they transition to adulthood, Dr. Hausmann explained. “The earlier the kids develop the skills to discuss their medicines, their side effects, the better they’ll be able to transition to adult medicine,” he said.
For the patients who go into remission and stay in remission, the message is also important. “To have the reassurance that a lot of those kids won’t be having active joint symptoms or need to be on medication, that’s a huge positive message that can get out there, so I think that’s great,” Dr. Imundo said.
Time to move on from ILAR classification?
Another big takeaway from the study was how patients’ ILAR classification changed across the 18-year follow-up. First proposed in 1995, the JIA ILAR classification has been revised several times for clarification purposes. In its current form, the ILAR classification considers a patient’s history when categorizing JIA types but also includes factors such as immediate family history. This system of assessing JIA has been criticized and there are initiatives to create a new JIA classification system to replace it.
“The ILAR criteria were designed to classify patients 6 months after disease onset in an attempt to find some commonality in clinical phenotypes, prognosis, and suggested management,” Dr. Wahezi said. “While there continues to be debate as to whether we can improve our classification of JIA patients, it is not surprising that phenotypes may evolve over time as new clinical features develop. As pediatric rheumatologists, we are well accustomed to having to modify management plans as children manifest with new clinical features over time.”
Although the percentage of patients who switched ILAR classifications over the study period was “much higher” than she would have thought, Dr. Imundo said it was the reasons provided in the study that seemed odd to her. “The classification scheme relies on your family history, like someone else in your family now has psoriasis, so your arthritis classification changes,” she explained.
“We want to head toward a much more unified classification scheme, a simpler one. We now understand that some of the diseases that we see in pediatrics are really the equivalent or same disease in adults,” she said.
“Most of the pediatric categories of JIA have distinct adult correlates,” Dr. Hausmann agreed. RF-positive polyarthritis in children and rheumatoid arthritis in adults are correlated, as are systemic JIA and adult-onset Still’s disease, he explained. “That has been borne out also by genetic susceptibility studies that the genetic predispositions to systemic arthritis in children is the same as the genetic predisposition to adult-onset Still’s disease in adults. By and large, there are a lot of similarities between the two.
“I think we need to incorporate some of that knowledge in better classifying kids with JIA so that we can find the best treatments and the best outcomes, and we can provide information to families about the expected course of the disease over time so that can inform our discussions.”
Some pediatric rheumatologists accept the classification system is flawed, but not all concur with the degree to which these problems impact patient care. “While the ILAR classification criteria may be subject to criticism, it does provide general context and prognostic implications for patients and families,” Dr. Wahezi said.
“The medicines certainly are very similar across the JIA categories, so the implications are not as broad” when classification changes,” Dr. Hausmann said. “But it certainly shows that there are things that we still don’t know. I think classification is actually pretty important because it might give you a sense of how persistent the disease will be.”
Dr. Imundo said the ILAR classification’s “time is limited,” and rheumatologists may soon need to adopt a new way of classifying children with rheumatic disease – “a more data-driven, genetics-driven scheme.”
“These categories are so imperfect, and the patients are changing. I feel like that says to me, let’s find something that’s more predictive that really helps us a little better than what we have now,” she said.
The study had no specific funding. The authors of the study and the editorial have disclosed no relevant financial relationships. Dr. Hausmann reports receiving salary support from CARRA. Dr. Imundo and Dr. Wahezi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
“Children are not little adults” is a common refrain in pediatric medicine, but when it comes to a condition like juvenile idiopathic arthritis (JIA), rheumatologists might be better off treating pediatric and adult rheumatic disease more similarly.
A recent study published in Arthritis Care & Research followed children diagnosed with JIA for 18 years. Although not the first long-term study to examine children with JIA, it is unique in that it took place “during a time where biologic DMARDs [disease-modifying antirheumatic drugs] were emerging as a fundamental therapy in the management of children with JIA,” said Dawn M. Wahezi, MD, chief of the division of pediatric rheumatology at the Children’s Hospital at Montefiore in New York, who was not involved with the study.
Additionally, the study highlights the International League of Associations for Rheumatology (ILAR) consensus-based classification criteria as an imperfect method to categorize patients with JIA.
Mia Glerup, MD, PhD, of the department of pediatrics at Aarhus (Denmark) University Hospital and colleagues prospectively analyzed 373 patients from Denmark, Norway, Sweden, and Finland with new-onset JIA between 1997 and 2000 and evaluated them at baseline, 8 years, and 18 years. At each visit, the researchers collected data on demographics, disease activity, ILAR category, treatment, and blood samples.
Patients in the cohort were mostly girls (66.7%) with a median age of 5.9 years at onset. Approximately one-third (34.8%) of patients were antinuclear antibody (ANA) positive and 21.6% were HLA-B27 positive. The most common JIA categories at baseline were persistent oligoarthritis (53.9%), polyarticular rheumatoid factor (RF) negative (21.1%), and undifferentiated arthritis (10.2%).
Dr. Glerup and colleagues found that the proportion of patients not receiving DMARDs declined from 73.2% at baseline to 59.7% at 8 years, and then rose again to 70% at 18 years (risk ratio, 1.3; P = .003). The group of 103 patients who used conventional DMARDs (cDMARDs) either as monotherapy or in combination with a biologic DMARD (bDMARD) at 8 years dwindled to 44 (42.7%) at 18 years (RR, 0.4; P < .001), whereas 32 of 52 patients (61.5%) using bDMARDs at 8 years were still taking them at 18 years (RR, 0.6; P = .02). Across the whole study, 14.7% of patients never received any JIA treatment, and 33 of 85 patients (38.8%) on continuous DMARDs developed uveitis during the study period.
Overall, 62.7% of patients received DMARDs at least once, including 89.7% with polyarticular RF negative, 77.3% with oligoarticular extended, 76.9% with systemic, 75.7% with juvenile enthesitis-related arthritis (ERA), 66.7% with polyarticular RF-positive, 65.2% with juvenile psoriatic arthritis (JPsA), 58.9% with undifferentiated JIA, and 27.6% of patients with persistent oligoarticular disease.
The median number of active joints dropped from 3 (range, 1-30) at baseline to 0 at 8 years (range, 0-13), whereas the median cumulative number of affected joints rose from 3 at baseline (range, 1-30) to 6 at 8 years (range, 1-41). At last follow-up, the median number of active joints was 0 (range, 0-5) and median cumulative number of affected joints was 7 (range, 1-47). The percentage of patients in remission barely changed from 52% at 8 years to 51% at 18.
Some patients also changed ILAR categories during the study period, with 7% shifting between baseline and 8 years, and 11% shifting between 8-year and 18-year follow-up. Compared with baseline, by the 18-year follow-up time point there was a significant decrease in the number of patients categorized as oligoarticular (230 vs. 197 patients; P = .02), a significant increase in patients in the psoriatic ILAR category (8 vs. 28 patients; P < .001), and a nonsignificant increase in the number of patients in the undifferentiated category (45 vs. 63 patients; P = .06).
“Almost half of the changes in the distribution between the ILAR categories were caused by updated information on heredity in a first-degree relative obtained at the follow-up visits,” Dr. Glerup and colleagues write.
The results of the long-term study show that patients are “likely to remain in remission – with the converse also evident, as patients still with evidence of disease activity at 8 years after disease onset were more likely to have refractory disease,” Dr. Wahezi said.
Commenting on the study’s findings, Lisa F. Imundo, MD, director of adolescent rheumatology at Columbia University Medical Center in New York, said they are “great news to be able to give parents of young kids with arthritis.” However, she questioned whether the results are generalizable to populations of patients “who are in the worst prognostic group.”
For example, a substantial proportion of patients were classified under the oligoarticular category. “That’s already a group that we know from experience tends to have a better outcome than some of the other groups of JIA,” she said.
“That kind of weaves its way through the whole study, because then they show a lot of patients have come off their medication. Patients who had more severe disease in more joints would be less likely, I think, to just stop their medication and stop going to doctors,” Dr. Imundo explained.
Although the study is valuable for its long-term follow-up, there is also a question of generalizability across a more diverse ethnic and racial group. The authors do not elaborate on the racial breakdown of their patients, Dr. Imundo said, “so we’re going to have to assume that the vast majority are going to [have] Caucasian Nordic ethnic background, and that goes along with them having this high percentage of HLA-B27 positivity, which is a gene that’s more prevalent in northern European populations.”
Jonathan Hausmann, MD, a pediatric and adult rheumatologist at Boston Children’s Hospital, Boston,, told this news organization that he believes the overall conclusions from the study – that JIA persists over time and that ILAR classification is a somewhat imprecise measure of assessing JIA types in children – would be generalizable to other groups.
However, long-term registries evaluating JIA in more diverse populations, such as the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry, could confirm these results, said Dr. Hausmann, who is a registry informatics associate with CARRA and was not associated with the research.
Long-term management of JIA
In an accompanying editorial, Jaime Guzman, MD, MSc, and Ross E. Petty, MD, PhD, of British Columbia Children’s Hospital and the University of British Columbia, Vancouver, said a rheumatologist’s interpretation of the study would be tied to what they learned about children with arthritis in medical school. They would see the glass as “half full” if children who achieved remission stayed in remission if they learned that a child might end up outgrowing JIA but potentially develop lifelong disability, whereas others may focus on the outcome of approximately half of patients not achieving remission.
“When I was going through medical school, I remember learning that JIA is a disease of children, and typically, they outgrow it as they become adults,” Dr. Hausmann said. “I think this study and many other studies have shown that that’s actually not the case – that, in fact, it may be a majority of kids continue having active disease even through adulthood.”
If a rheumatologist knows JIA is likely to continue into adulthood, “that’s huge,” Dr. Hausmann said. “That means when we first diagnose patients with JIA as kids, we need to set expectations with the families that this may not just go away; this may be something that could be more lifelong.”
Education on the part of the patient, their parents, and their clinician on the expected trajectory of the disease is critical so that children can continue their own care as they transition to adulthood, Dr. Hausmann explained. “The earlier the kids develop the skills to discuss their medicines, their side effects, the better they’ll be able to transition to adult medicine,” he said.
For the patients who go into remission and stay in remission, the message is also important. “To have the reassurance that a lot of those kids won’t be having active joint symptoms or need to be on medication, that’s a huge positive message that can get out there, so I think that’s great,” Dr. Imundo said.
Time to move on from ILAR classification?
Another big takeaway from the study was how patients’ ILAR classification changed across the 18-year follow-up. First proposed in 1995, the JIA ILAR classification has been revised several times for clarification purposes. In its current form, the ILAR classification considers a patient’s history when categorizing JIA types but also includes factors such as immediate family history. This system of assessing JIA has been criticized and there are initiatives to create a new JIA classification system to replace it.
“The ILAR criteria were designed to classify patients 6 months after disease onset in an attempt to find some commonality in clinical phenotypes, prognosis, and suggested management,” Dr. Wahezi said. “While there continues to be debate as to whether we can improve our classification of JIA patients, it is not surprising that phenotypes may evolve over time as new clinical features develop. As pediatric rheumatologists, we are well accustomed to having to modify management plans as children manifest with new clinical features over time.”
Although the percentage of patients who switched ILAR classifications over the study period was “much higher” than she would have thought, Dr. Imundo said it was the reasons provided in the study that seemed odd to her. “The classification scheme relies on your family history, like someone else in your family now has psoriasis, so your arthritis classification changes,” she explained.
“We want to head toward a much more unified classification scheme, a simpler one. We now understand that some of the diseases that we see in pediatrics are really the equivalent or same disease in adults,” she said.
“Most of the pediatric categories of JIA have distinct adult correlates,” Dr. Hausmann agreed. RF-positive polyarthritis in children and rheumatoid arthritis in adults are correlated, as are systemic JIA and adult-onset Still’s disease, he explained. “That has been borne out also by genetic susceptibility studies that the genetic predispositions to systemic arthritis in children is the same as the genetic predisposition to adult-onset Still’s disease in adults. By and large, there are a lot of similarities between the two.
“I think we need to incorporate some of that knowledge in better classifying kids with JIA so that we can find the best treatments and the best outcomes, and we can provide information to families about the expected course of the disease over time so that can inform our discussions.”
Some pediatric rheumatologists accept the classification system is flawed, but not all concur with the degree to which these problems impact patient care. “While the ILAR classification criteria may be subject to criticism, it does provide general context and prognostic implications for patients and families,” Dr. Wahezi said.
“The medicines certainly are very similar across the JIA categories, so the implications are not as broad” when classification changes,” Dr. Hausmann said. “But it certainly shows that there are things that we still don’t know. I think classification is actually pretty important because it might give you a sense of how persistent the disease will be.”
Dr. Imundo said the ILAR classification’s “time is limited,” and rheumatologists may soon need to adopt a new way of classifying children with rheumatic disease – “a more data-driven, genetics-driven scheme.”
“These categories are so imperfect, and the patients are changing. I feel like that says to me, let’s find something that’s more predictive that really helps us a little better than what we have now,” she said.
The study had no specific funding. The authors of the study and the editorial have disclosed no relevant financial relationships. Dr. Hausmann reports receiving salary support from CARRA. Dr. Imundo and Dr. Wahezi have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ARTHRITIS CARE & RESEARCH
Unfavorable intermediate-risk prostate cancer: EBRT plus BT improve survival
Key clinical point: External beam radiotherapy (EBRT) plus brachytherapy (BT) boost improves survival in patients with unfavorable intermediate-risk prostate cancer vs. brachytherapy alone.
Major finding: The median follow-up was 68 months. In weight-adjusted analysis, EBRT plus BT (hazard ratio [HR] 0.82; P = .000005) vs. BT alone significantly improves overall survival (OS). At 10 years, the OS rate was 62.4% and 69.3% in the BT alone and EBRT plus BT groups, respectively (P < .0001).
Study details: This was a retrospective study of 11,721 patients with unfavorable intermediate-risk prostate cancer diagnosed between 2004 and 2015. The patients received either definitive BT without androgen deprivation therapy (ADT), BT with ADT, EBRT with ADT, or EBRT with BT and ADT.
Disclosures: This work was supported by Washington University in St. Louis Medical School and Barnes Jewish Hospital. The authors received advisory/consulting/scientific fees and honoraria outside this work.
Source: Andruska N et al. Brachytherapy. 2022 (Feb 2). Doi: 10.1016/j.brachy.2021.12.008.
Key clinical point: External beam radiotherapy (EBRT) plus brachytherapy (BT) boost improves survival in patients with unfavorable intermediate-risk prostate cancer vs. brachytherapy alone.
Major finding: The median follow-up was 68 months. In weight-adjusted analysis, EBRT plus BT (hazard ratio [HR] 0.82; P = .000005) vs. BT alone significantly improves overall survival (OS). At 10 years, the OS rate was 62.4% and 69.3% in the BT alone and EBRT plus BT groups, respectively (P < .0001).
Study details: This was a retrospective study of 11,721 patients with unfavorable intermediate-risk prostate cancer diagnosed between 2004 and 2015. The patients received either definitive BT without androgen deprivation therapy (ADT), BT with ADT, EBRT with ADT, or EBRT with BT and ADT.
Disclosures: This work was supported by Washington University in St. Louis Medical School and Barnes Jewish Hospital. The authors received advisory/consulting/scientific fees and honoraria outside this work.
Source: Andruska N et al. Brachytherapy. 2022 (Feb 2). Doi: 10.1016/j.brachy.2021.12.008.
Key clinical point: External beam radiotherapy (EBRT) plus brachytherapy (BT) boost improves survival in patients with unfavorable intermediate-risk prostate cancer vs. brachytherapy alone.
Major finding: The median follow-up was 68 months. In weight-adjusted analysis, EBRT plus BT (hazard ratio [HR] 0.82; P = .000005) vs. BT alone significantly improves overall survival (OS). At 10 years, the OS rate was 62.4% and 69.3% in the BT alone and EBRT plus BT groups, respectively (P < .0001).
Study details: This was a retrospective study of 11,721 patients with unfavorable intermediate-risk prostate cancer diagnosed between 2004 and 2015. The patients received either definitive BT without androgen deprivation therapy (ADT), BT with ADT, EBRT with ADT, or EBRT with BT and ADT.
Disclosures: This work was supported by Washington University in St. Louis Medical School and Barnes Jewish Hospital. The authors received advisory/consulting/scientific fees and honoraria outside this work.
Source: Andruska N et al. Brachytherapy. 2022 (Feb 2). Doi: 10.1016/j.brachy.2021.12.008.
Intermediate-/high-risk prostate cancer: Focal HIFU provides good control
Key clinical point: Focal high-intensity focused ultrasound (HIFU) shows good cancer control in patients with nonmetastatic prostate cancer.
Major finding: At 7 years, failure-free survival was 69% (95% CI 64%-74%). In patients with intermediate- and high-risk cancers, failure-free survival at 7 years was 68% (95% CI 62%-75%) and 65% (95% CI 56%-74%), respectively.
Study details: This was a study of 1,379 patients with nonmetastatic prostate cancer including intermediate- (65%) and high-risk (28%) categories from a prospective registry who received focal therapy using HIFU during 2005-2020.
Disclosures: This work was supported by Sonacare Inc. The authors received research funding, consulting/advisory fees, and travel grants. Some of the authors were paid proctors to give training on the procedures.
Source: Reddy D et al. Eur Urol. 2022 (Feb 3). Doi: 10.1016/j.eururo.2022.01.005.
Key clinical point: Focal high-intensity focused ultrasound (HIFU) shows good cancer control in patients with nonmetastatic prostate cancer.
Major finding: At 7 years, failure-free survival was 69% (95% CI 64%-74%). In patients with intermediate- and high-risk cancers, failure-free survival at 7 years was 68% (95% CI 62%-75%) and 65% (95% CI 56%-74%), respectively.
Study details: This was a study of 1,379 patients with nonmetastatic prostate cancer including intermediate- (65%) and high-risk (28%) categories from a prospective registry who received focal therapy using HIFU during 2005-2020.
Disclosures: This work was supported by Sonacare Inc. The authors received research funding, consulting/advisory fees, and travel grants. Some of the authors were paid proctors to give training on the procedures.
Source: Reddy D et al. Eur Urol. 2022 (Feb 3). Doi: 10.1016/j.eururo.2022.01.005.
Key clinical point: Focal high-intensity focused ultrasound (HIFU) shows good cancer control in patients with nonmetastatic prostate cancer.
Major finding: At 7 years, failure-free survival was 69% (95% CI 64%-74%). In patients with intermediate- and high-risk cancers, failure-free survival at 7 years was 68% (95% CI 62%-75%) and 65% (95% CI 56%-74%), respectively.
Study details: This was a study of 1,379 patients with nonmetastatic prostate cancer including intermediate- (65%) and high-risk (28%) categories from a prospective registry who received focal therapy using HIFU during 2005-2020.
Disclosures: This work was supported by Sonacare Inc. The authors received research funding, consulting/advisory fees, and travel grants. Some of the authors were paid proctors to give training on the procedures.
Source: Reddy D et al. Eur Urol. 2022 (Feb 3). Doi: 10.1016/j.eururo.2022.01.005.
Beta-blocker use at surgery lowers prostate cancer recurrence risk
Key clinical point: Use of nonselective beta-blockers at the time of radical prostatectomy is associated with a lower odds of treatment initiation for recurrence in patients with prostate cancer.
Major finding: The use of nonselective beta-blockers at the time of surgery was associated with a significantly lower odds of treatment for cancer recurrence (adjusted hazard ratio 0.64; P = .03). The most common nonselective beta-blockers used were carvedilol (56.9%) and propranolol (25.4%).
Study details: This was a retrospective cohort study of 11,117 patients with prostate cancer who underwent radical prostatectomy between 2008 and 2015.
Disclosures: This study was supported by the Norwegian Cancer Society. The authors received grants from the Norwegian Cancer Society during this work.
Source: Sivanesan S et al. JAMA Netw Open. 2022 (Jan 26). Doi: 10.1001/jamanetworkopen.2021.45230.
Key clinical point: Use of nonselective beta-blockers at the time of radical prostatectomy is associated with a lower odds of treatment initiation for recurrence in patients with prostate cancer.
Major finding: The use of nonselective beta-blockers at the time of surgery was associated with a significantly lower odds of treatment for cancer recurrence (adjusted hazard ratio 0.64; P = .03). The most common nonselective beta-blockers used were carvedilol (56.9%) and propranolol (25.4%).
Study details: This was a retrospective cohort study of 11,117 patients with prostate cancer who underwent radical prostatectomy between 2008 and 2015.
Disclosures: This study was supported by the Norwegian Cancer Society. The authors received grants from the Norwegian Cancer Society during this work.
Source: Sivanesan S et al. JAMA Netw Open. 2022 (Jan 26). Doi: 10.1001/jamanetworkopen.2021.45230.
Key clinical point: Use of nonselective beta-blockers at the time of radical prostatectomy is associated with a lower odds of treatment initiation for recurrence in patients with prostate cancer.
Major finding: The use of nonselective beta-blockers at the time of surgery was associated with a significantly lower odds of treatment for cancer recurrence (adjusted hazard ratio 0.64; P = .03). The most common nonselective beta-blockers used were carvedilol (56.9%) and propranolol (25.4%).
Study details: This was a retrospective cohort study of 11,117 patients with prostate cancer who underwent radical prostatectomy between 2008 and 2015.
Disclosures: This study was supported by the Norwegian Cancer Society. The authors received grants from the Norwegian Cancer Society during this work.
Source: Sivanesan S et al. JAMA Netw Open. 2022 (Jan 26). Doi: 10.1001/jamanetworkopen.2021.45230.
Prostate cancer: ACEi use during radiotherapy may protect against hematuria
Key clinical point: Angiotensin-converting enzyme inhibitors (ACEi) use during radiotherapy is associated with a lower risk for hematuria in patients with prostate cancer. The effect was independent of clinical factors associated with late hematuria.
Major finding: The cumulative probability of hematuria at 4 years in patients receiving ACEi during radiotherapy was significantly lower vs. nonusers (4.8% vs. 16.5%). The risk for hematuria was significantly lower in patients receiving ACEi (adjusted hazard ratio 0.51; P = .030) after adjusting for clinical factors associated with hematuria.
Study details: This article reported on two multicenter observational studies, URWCI (n = 256) and REQUITE (n = 1,437), of patients with prostate cancer undergoing radiotherapy.
Disclosures: This work was supported by the National Cancer Institute, University of Rochester Wilmot Cancer Institute, Cancer Research UK, and others. The authors reported no competing interests.
Source: Kerns SL et al. Radiother Oncol. 2022;168:P75-82 (Jan 22). Doi: 10.1016/j.radonc.2022.01.014.
Key clinical point: Angiotensin-converting enzyme inhibitors (ACEi) use during radiotherapy is associated with a lower risk for hematuria in patients with prostate cancer. The effect was independent of clinical factors associated with late hematuria.
Major finding: The cumulative probability of hematuria at 4 years in patients receiving ACEi during radiotherapy was significantly lower vs. nonusers (4.8% vs. 16.5%). The risk for hematuria was significantly lower in patients receiving ACEi (adjusted hazard ratio 0.51; P = .030) after adjusting for clinical factors associated with hematuria.
Study details: This article reported on two multicenter observational studies, URWCI (n = 256) and REQUITE (n = 1,437), of patients with prostate cancer undergoing radiotherapy.
Disclosures: This work was supported by the National Cancer Institute, University of Rochester Wilmot Cancer Institute, Cancer Research UK, and others. The authors reported no competing interests.
Source: Kerns SL et al. Radiother Oncol. 2022;168:P75-82 (Jan 22). Doi: 10.1016/j.radonc.2022.01.014.
Key clinical point: Angiotensin-converting enzyme inhibitors (ACEi) use during radiotherapy is associated with a lower risk for hematuria in patients with prostate cancer. The effect was independent of clinical factors associated with late hematuria.
Major finding: The cumulative probability of hematuria at 4 years in patients receiving ACEi during radiotherapy was significantly lower vs. nonusers (4.8% vs. 16.5%). The risk for hematuria was significantly lower in patients receiving ACEi (adjusted hazard ratio 0.51; P = .030) after adjusting for clinical factors associated with hematuria.
Study details: This article reported on two multicenter observational studies, URWCI (n = 256) and REQUITE (n = 1,437), of patients with prostate cancer undergoing radiotherapy.
Disclosures: This work was supported by the National Cancer Institute, University of Rochester Wilmot Cancer Institute, Cancer Research UK, and others. The authors reported no competing interests.
Source: Kerns SL et al. Radiother Oncol. 2022;168:P75-82 (Jan 22). Doi: 10.1016/j.radonc.2022.01.014.
Obesity is linked to high-risk prostate cancer in multiethnic population
Key clinical point: Obesity (body mass index of ≥30 kg/m2) is associated with high-risk prostate cancer in non-Hispanic Black (NHB) and Hispanic men.
Major finding: Obesity showed an independent association with high-risk prostate cancer (odds ratio [OR] 2.23; 95% CI 1.28-3.81). Compared with nonobese men without diabetes mellitus (DM), those with obesity and DM showed a higher risk for intermediate- (OR 1.93; P = .013) and high-risk prostate cancer (OR 2.40; P = .011).
Study details: This was a retrospective study of 1,303 patients with prostate cancer. The prevalence of obesity and DM was 29.3% and 28.3%, respectively. Most of the patients were of NHB (38%) or Hispanic ethnicity (31%).
Disclosures: This work was funded by the American Cancer Society. The authors declared no conflicts of interest.
Source: Zhu D et al. Clin Genitourin Cancer. 2022 (Jan 31). Doi: 10.1016/j.clgc.2022.01.016.
Key clinical point: Obesity (body mass index of ≥30 kg/m2) is associated with high-risk prostate cancer in non-Hispanic Black (NHB) and Hispanic men.
Major finding: Obesity showed an independent association with high-risk prostate cancer (odds ratio [OR] 2.23; 95% CI 1.28-3.81). Compared with nonobese men without diabetes mellitus (DM), those with obesity and DM showed a higher risk for intermediate- (OR 1.93; P = .013) and high-risk prostate cancer (OR 2.40; P = .011).
Study details: This was a retrospective study of 1,303 patients with prostate cancer. The prevalence of obesity and DM was 29.3% and 28.3%, respectively. Most of the patients were of NHB (38%) or Hispanic ethnicity (31%).
Disclosures: This work was funded by the American Cancer Society. The authors declared no conflicts of interest.
Source: Zhu D et al. Clin Genitourin Cancer. 2022 (Jan 31). Doi: 10.1016/j.clgc.2022.01.016.
Key clinical point: Obesity (body mass index of ≥30 kg/m2) is associated with high-risk prostate cancer in non-Hispanic Black (NHB) and Hispanic men.
Major finding: Obesity showed an independent association with high-risk prostate cancer (odds ratio [OR] 2.23; 95% CI 1.28-3.81). Compared with nonobese men without diabetes mellitus (DM), those with obesity and DM showed a higher risk for intermediate- (OR 1.93; P = .013) and high-risk prostate cancer (OR 2.40; P = .011).
Study details: This was a retrospective study of 1,303 patients with prostate cancer. The prevalence of obesity and DM was 29.3% and 28.3%, respectively. Most of the patients were of NHB (38%) or Hispanic ethnicity (31%).
Disclosures: This work was funded by the American Cancer Society. The authors declared no conflicts of interest.
Source: Zhu D et al. Clin Genitourin Cancer. 2022 (Jan 31). Doi: 10.1016/j.clgc.2022.01.016.
Prostate cancer: Active surveillance may be appropriate in selected intermediate-risk patients
Key clinical point: The risk for metastasis and cancer-specific mortality is significantly higher in patients with favorable and unfavorable intermediate-risk vs. low-risk patients with prostate cancer managed with active surveillance.
Major finding: The risk for metastasis and prostate cancer-specific mortality was significantly higher in patients with favorable (subdistribution hazard ratios [SHR] 6.49 and 2.94, respectively; both P < .001) and unfavorable (SHR 14.45 and 7.90, respectively; P < .001) intermediate-risk disease vs. those with low-risk disease.
Study details: This was a retrospective study of 9,733 patients with low- or intermediate-risk prostate cancer undergoing active surveillance between 2001 and 2015.
Disclosures: This study was sponsored by the National Institutes of Health and U.S. Department of Defense. Several of the authors received consulting/speaker fees, honoraria, travel support, and other financial and nonfinancial interests, served on advisory boards, or were employed by pharmaceutical companies. The other authors had no conflicts of interest.
Source: Courtney PT et al. J Natl Compr Canc Netw. 2022;20(2):151-159 (Feb 1). Doi: 10.6004/jnccn.2021.7065.
Key clinical point: The risk for metastasis and cancer-specific mortality is significantly higher in patients with favorable and unfavorable intermediate-risk vs. low-risk patients with prostate cancer managed with active surveillance.
Major finding: The risk for metastasis and prostate cancer-specific mortality was significantly higher in patients with favorable (subdistribution hazard ratios [SHR] 6.49 and 2.94, respectively; both P < .001) and unfavorable (SHR 14.45 and 7.90, respectively; P < .001) intermediate-risk disease vs. those with low-risk disease.
Study details: This was a retrospective study of 9,733 patients with low- or intermediate-risk prostate cancer undergoing active surveillance between 2001 and 2015.
Disclosures: This study was sponsored by the National Institutes of Health and U.S. Department of Defense. Several of the authors received consulting/speaker fees, honoraria, travel support, and other financial and nonfinancial interests, served on advisory boards, or were employed by pharmaceutical companies. The other authors had no conflicts of interest.
Source: Courtney PT et al. J Natl Compr Canc Netw. 2022;20(2):151-159 (Feb 1). Doi: 10.6004/jnccn.2021.7065.
Key clinical point: The risk for metastasis and cancer-specific mortality is significantly higher in patients with favorable and unfavorable intermediate-risk vs. low-risk patients with prostate cancer managed with active surveillance.
Major finding: The risk for metastasis and prostate cancer-specific mortality was significantly higher in patients with favorable (subdistribution hazard ratios [SHR] 6.49 and 2.94, respectively; both P < .001) and unfavorable (SHR 14.45 and 7.90, respectively; P < .001) intermediate-risk disease vs. those with low-risk disease.
Study details: This was a retrospective study of 9,733 patients with low- or intermediate-risk prostate cancer undergoing active surveillance between 2001 and 2015.
Disclosures: This study was sponsored by the National Institutes of Health and U.S. Department of Defense. Several of the authors received consulting/speaker fees, honoraria, travel support, and other financial and nonfinancial interests, served on advisory boards, or were employed by pharmaceutical companies. The other authors had no conflicts of interest.
Source: Courtney PT et al. J Natl Compr Canc Netw. 2022;20(2):151-159 (Feb 1). Doi: 10.6004/jnccn.2021.7065.
Prostate cancer: Salvage radiotherapy after surgery extends long-term survival
Key clinical point: In patients with prostate cancer, salvage radiotherapy (SRT) for biochemical recurrence after radical prostatectomy is associated with improved survival in the long term.
Major finding: The median follow up was 95.9 months. At 15 years, SRT was associated with a significantly higher metastasis-free survival (84.3% vs. 76.9%; adjusted hazard ratio [aHR] 0.37; P < .001) and overall survival (85.3% vs. 74.4%; aHR 0.64; P = .03).
Study details: A propensity score-matched analysis of 874 patients with prostate cancer who experienced biochemical recurrence after radical prostatectomy and underwent SRT or observation between 1989 and 2016.
Disclosures: No external funding source was identified for this work. The authors declared no conflicts of interest.
Source: Tilki D et al. Cancers. 2022;14(3):740 (Jan 31). Doi: 10.3390/cancers14030740.
Key clinical point: In patients with prostate cancer, salvage radiotherapy (SRT) for biochemical recurrence after radical prostatectomy is associated with improved survival in the long term.
Major finding: The median follow up was 95.9 months. At 15 years, SRT was associated with a significantly higher metastasis-free survival (84.3% vs. 76.9%; adjusted hazard ratio [aHR] 0.37; P < .001) and overall survival (85.3% vs. 74.4%; aHR 0.64; P = .03).
Study details: A propensity score-matched analysis of 874 patients with prostate cancer who experienced biochemical recurrence after radical prostatectomy and underwent SRT or observation between 1989 and 2016.
Disclosures: No external funding source was identified for this work. The authors declared no conflicts of interest.
Source: Tilki D et al. Cancers. 2022;14(3):740 (Jan 31). Doi: 10.3390/cancers14030740.
Key clinical point: In patients with prostate cancer, salvage radiotherapy (SRT) for biochemical recurrence after radical prostatectomy is associated with improved survival in the long term.
Major finding: The median follow up was 95.9 months. At 15 years, SRT was associated with a significantly higher metastasis-free survival (84.3% vs. 76.9%; adjusted hazard ratio [aHR] 0.37; P < .001) and overall survival (85.3% vs. 74.4%; aHR 0.64; P = .03).
Study details: A propensity score-matched analysis of 874 patients with prostate cancer who experienced biochemical recurrence after radical prostatectomy and underwent SRT or observation between 1989 and 2016.
Disclosures: No external funding source was identified for this work. The authors declared no conflicts of interest.
Source: Tilki D et al. Cancers. 2022;14(3):740 (Jan 31). Doi: 10.3390/cancers14030740.
Localized prostate cancer: Add-on ADT delays metastasis
Key clinical point: Adding androgen deprivation therapy (ADT) to radiotherapy in men with intermediate-/high-risk localized prostate cancer improves metastasis-free survival (MFS).
Major finding: At a median follow-up of 11.4 years, the addition of ADT to radiotherapy significantly improved MFS (hazard ratio [HR] 0.83; P < .0001). Prolonged adjuvant ADT also improved MFS (HR 0.84; P < .0001).
Study details: This was an individual patient data meta-analysis of 10,853 patients with localized prostate cancer from 12 randomized trials.
Disclosures: This work was funded by the University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology. The authors received personal/consulting/advisory fees and research support or reported being a member of the clinical trial steering committee and holding stocks outside this work.
Source: Kishan AU et al. Lancet Oncol. 2022;23(2):P304-16 (Jan 17). Doi: 10.1016/ S1470-2045(21)00705-1.
Key clinical point: Adding androgen deprivation therapy (ADT) to radiotherapy in men with intermediate-/high-risk localized prostate cancer improves metastasis-free survival (MFS).
Major finding: At a median follow-up of 11.4 years, the addition of ADT to radiotherapy significantly improved MFS (hazard ratio [HR] 0.83; P < .0001). Prolonged adjuvant ADT also improved MFS (HR 0.84; P < .0001).
Study details: This was an individual patient data meta-analysis of 10,853 patients with localized prostate cancer from 12 randomized trials.
Disclosures: This work was funded by the University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology. The authors received personal/consulting/advisory fees and research support or reported being a member of the clinical trial steering committee and holding stocks outside this work.
Source: Kishan AU et al. Lancet Oncol. 2022;23(2):P304-16 (Jan 17). Doi: 10.1016/ S1470-2045(21)00705-1.
Key clinical point: Adding androgen deprivation therapy (ADT) to radiotherapy in men with intermediate-/high-risk localized prostate cancer improves metastasis-free survival (MFS).
Major finding: At a median follow-up of 11.4 years, the addition of ADT to radiotherapy significantly improved MFS (hazard ratio [HR] 0.83; P < .0001). Prolonged adjuvant ADT also improved MFS (HR 0.84; P < .0001).
Study details: This was an individual patient data meta-analysis of 10,853 patients with localized prostate cancer from 12 randomized trials.
Disclosures: This work was funded by the University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and the American Society for Radiation Oncology. The authors received personal/consulting/advisory fees and research support or reported being a member of the clinical trial steering committee and holding stocks outside this work.
Source: Kishan AU et al. Lancet Oncol. 2022;23(2):P304-16 (Jan 17). Doi: 10.1016/ S1470-2045(21)00705-1.