Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Among high-risk early breast cancer patients, delivery of a radiation boost to the tumor bed during whole breast irradiation was just as safe and effective as delivering the boost sequentially after whole breast irradiation ended. The findings from the phase 3 clinical trial are a boon to patient convenience.

“These findings are indeed practice changing. This was a well-designed trial that looked at shortening treatment from six to three weeks. They showed equivalent local control and importantly, a good cosmetic outcome over time,” said Kathleen Horst, MD, who served as a discussant during a presentation given by Frank Vicini, MD, FASTRO, GenesisCare, during the annual meeting of the American Society for Radiation Oncology.

“This is substantially more convenient. It’s cost effective both for the health care system and individual patients. Importantly, our patients come in for treatment every day and they’re taking time from work which means they have to arrange for childcare and transportation. So, this makes a big difference for these patients,” said Dr. Horst, who is a professor of radiation oncology at Stanford (Calif.) Medicine and director of well-being in the radiation department at Stanford Medicine.

“One of the things that was surprising is that I think all of us were thinking this might be a more toxic regimen, but as Dr. Vicini showed, it was equally effective over time with minimal toxicity and cosmesis was stable over time, which is important. Importantly, it included patient-reported outcomes, not just the physician-reported outcomes. Broadly, I think these findings are applicable for many patients, including all patients who are receiving whole breast radiotherapy with an added boost. I think over time this is going to improve the quality of life of our patients. It represents an innovative change that everyone is going to be excited to embrace,” Dr. Horst said.

Previous randomized controlled trials showed that an additional radiation dose to the tumor bed following lumpectomy and whole breast irradiation reduces the relative risk of local recurrence by about 35%. However, this increases treatment time for patients who have already endured an extensive regimen. For whole breast irradiation, hypofractionated radiation in 15-16 fractions over 3 weeks has comparable recurrence rates as a 5-week regimen, but the relevant trials did not examine the effect hypofractionation may have on a radiation boost to the tumor bed of high-risk patients. Because of this lack of evidence, current practice calls for the boost to remain sequential in five to eight fractions after completion of whole breast irradiation, which adds 1 week to a 1.5 week–long treatment.

The study included 2,262 patients who were randomized to receive a sequential boost or a concomitant boost. After a median follow-up of 7.4 years, there were 54 ipsilateral breast recurrence (IBR) events. The estimated 7-year risk of IBR was 2.2% in the sequential boost and 2.6% in the concurrent risk group (hazard ratio, 1.32; noninferiority test P = .039). Approximately 60% of patients received adjuvant chemotherapy.

Grade 3 or higher adverse events were similar with a frequency of 3.3% in the sequential group and 3.5% in the concurrent group (P = .79). The researchers used the Global Cosmetic Score (GCS) to assess outcomes from the perspective of both physicians and patients. 86% of physicians rated the outcome as excellent/good in the sequential group versus 82% in the concurrent group (P = .33).

“For high-risk early-stage breast cancer patients undergoing breast conservation, a concurrent boost with hypofractionated whole breast irradiation – compared to a sequential boost – results in noninferior local recurrence rates with no significant difference in toxicity, noninferior patient rated cosmesis, and no significant difference in physician rated cosmesis. The entire treatment was delivered in three weeks, even for high-risk patients. Just as critical, the use of target volume based radiation planning for [three-dimensional conformal or IMRT whole breast irradiation assessed by dose volume analysis is feasible, and resulted in very low toxicity in the treatment arms, regardless of the fractionation schedule, or the boost delivery,” Dr. Vincini said.

No conflicts of interest were disclosed for Dr. Horst or Dr. Vicini.

Neurofilament light chain (NfL) is a well-known and useful biomarker for multiple sclerosis (MS) disease activity, but its association with disease progression is not well understood. A new analysis of MS patients in California’s EPIC cohort suggests that NfL spikes occur about 1 year before clinical sign of MS disease worsening.

“We see evidence for accelerated neuroaxonal damage in the year preceding the first diagnosis of the progression events, [but] only if they were associated with evidence of focal inflammatory activity – that can be either clinical or imaging evidence,” said Ahmed Abdelhak, MD, during a presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“By the time we diagnose the EDSS progression, it’s already too late. Every damage or any accelerated neuroaxonal damage that has happened in association with this event already took place around a year ago. I think [this has] huge implications for the designing of clinical trials,” said Dr. Abdelhak, who is a postdoctoral researcher at the University of California, San Francisco.

In the study, researchers analyzed data from 609 MS cases, with a total of 3,906 office visits. The median age was 42 years, and 69.6% were female. Median disease duration was 6 years.

They examined the association between NfL scores and confirmed disease worsening, as recorded by an increase in EDSS score. There was an increase in NfL age-adjusted z score about 12 months in advance among patients with a progression association with a relapse in the past year, compared with individuals who did not experience disease progression. There was also a more modest increase among individuals who had disease progression without a recent relapse, but this was not statistically significant.

“Our findings suggest that the association between NfL levels and EDSS worsening is most prominent in the setting of relapse-associated events,” said Dr. Abdelhak.
 

Clinical implications and audience skepticism

During the Q&A following the talk, session moderator Charlotte Teunissen, PhD, professor of neurochemistry at Amsterdam University Medical Center, asked about the clinical implication of the finding. “It seems that you concluded that axonal damage has been done before the progression starts. Is that your conclusion? So it means that there is no option to interfere anymore, consequently.”

Dr. Abdelhak responded: “I think that’s a very important interpretation of the data, which I’m sure is a relatively new way of thinking about it. That means, indeed, that when we see these patients, measuring NfL wouldn’t deliver any additional value because they don’t differ between the groups at the time of EDSS worsening. And there is probably nothing more we can do about this event. But it’s still very important to know that any therapeutic intervention has also the need to prevent future disability progression, future neuroaxonal damage, but regarding what has happened already, I’m a little bit skeptical if we will be able to change anything.”

Dr. Teunissen expressed skepticism that there was no further neurodegeneration following the spike in NfL, and pointed out an important caveat, which was the study’s reliance on NfL. “You base your conclusions on what you observe for NfL, and it’s a far-fetched conclusion that there is no further axonal damage ongoing. Maybe NfL is just one marker, and it’s not the best biomarker to measure progression,” she said.

Dr. Abdelhak conceded that it will be necessary to confirm the findings with other biomarkers of neurological injury. Even different subunits of the NfL protein have been shown to have different dynamics in other neurological conditions. “So the data we have give definitely an incomplete picture because we [know] nothing about the other biomarkers of neuroaxonal injury, including the other subunits of NfL,” he said.

Later in the Q&A, Alasdair Coles, MD, professor of neurology at University of Cambridge (England), spoke from the audience. He suggested that the findings could be seen as dispiriting for clinicians. “Would the panel agree that actually for a clinician this is all rather disappointing, because none of these markers are telling us anything that we don’t otherwise know by examining the patient and doing scans?”

“I can attempt to tackle that provocative question,” replied Elias Sotirchos, MD, who also presented on an association between NfL and brain atrophy research during the session. He pointed out that all clinical tests are imperfect, and suggested that NfL isn’t something to be used in isolation. It could be useful when patients are experiencing new symptoms, or worsening symptoms, and in combination with MRI results. “My interpretation of NfL is that it does have incremental value, telling us which patients have lesions that are more destructive, potentially, given all of these consistent associations with brain atrophy and disability progression over time,” said Dr. Sotirchos, who is an assistant professor of neurology at Johns Hopkins Medicine, Baltimore.

Dr. Abdelhak and Dr. Teunissen have no relevant financial disclosures. Dr. Sotirchos has financial relationships with Alexion, Viela Bio, Horizon Therapeutics, Genentech, and Ad Scientiam.

Neurofilament light chain (NfL) is a well-known and useful biomarker for multiple sclerosis (MS) disease activity, but its association with disease progression is not well understood. A new analysis of MS patients in California’s EPIC cohort suggests that NfL spikes occur about 1 year before clinical sign of MS disease worsening.

“We see evidence for accelerated neuroaxonal damage in the year preceding the first diagnosis of the progression events, [but] only if they were associated with evidence of focal inflammatory activity – that can be either clinical or imaging evidence,” said Ahmed Abdelhak, MD, during a presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“By the time we diagnose the EDSS progression, it’s already too late. Every damage or any accelerated neuroaxonal damage that has happened in association with this event already took place around a year ago. I think [this has] huge implications for the designing of clinical trials,” said Dr. Abdelhak, who is a postdoctoral researcher at the University of California, San Francisco.

In the study, researchers analyzed data from 609 MS cases, with a total of 3,906 office visits. The median age was 42 years, and 69.6% were female. Median disease duration was 6 years.

They examined the association between NfL scores and confirmed disease worsening, as recorded by an increase in EDSS score. There was an increase in NfL age-adjusted z score about 12 months in advance among patients with a progression association with a relapse in the past year, compared with individuals who did not experience disease progression. There was also a more modest increase among individuals who had disease progression without a recent relapse, but this was not statistically significant.

“Our findings suggest that the association between NfL levels and EDSS worsening is most prominent in the setting of relapse-associated events,” said Dr. Abdelhak.
 

Clinical implications and audience skepticism

During the Q&A following the talk, session moderator Charlotte Teunissen, PhD, professor of neurochemistry at Amsterdam University Medical Center, asked about the clinical implication of the finding. “It seems that you concluded that axonal damage has been done before the progression starts. Is that your conclusion? So it means that there is no option to interfere anymore, consequently.”

Dr. Abdelhak responded: “I think that’s a very important interpretation of the data, which I’m sure is a relatively new way of thinking about it. That means, indeed, that when we see these patients, measuring NfL wouldn’t deliver any additional value because they don’t differ between the groups at the time of EDSS worsening. And there is probably nothing more we can do about this event. But it’s still very important to know that any therapeutic intervention has also the need to prevent future disability progression, future neuroaxonal damage, but regarding what has happened already, I’m a little bit skeptical if we will be able to change anything.”

Dr. Teunissen expressed skepticism that there was no further neurodegeneration following the spike in NfL, and pointed out an important caveat, which was the study’s reliance on NfL. “You base your conclusions on what you observe for NfL, and it’s a far-fetched conclusion that there is no further axonal damage ongoing. Maybe NfL is just one marker, and it’s not the best biomarker to measure progression,” she said.

Dr. Abdelhak conceded that it will be necessary to confirm the findings with other biomarkers of neurological injury. Even different subunits of the NfL protein have been shown to have different dynamics in other neurological conditions. “So the data we have give definitely an incomplete picture because we [know] nothing about the other biomarkers of neuroaxonal injury, including the other subunits of NfL,” he said.

Later in the Q&A, Alasdair Coles, MD, professor of neurology at University of Cambridge (England), spoke from the audience. He suggested that the findings could be seen as dispiriting for clinicians. “Would the panel agree that actually for a clinician this is all rather disappointing, because none of these markers are telling us anything that we don’t otherwise know by examining the patient and doing scans?”

“I can attempt to tackle that provocative question,” replied Elias Sotirchos, MD, who also presented on an association between NfL and brain atrophy research during the session. He pointed out that all clinical tests are imperfect, and suggested that NfL isn’t something to be used in isolation. It could be useful when patients are experiencing new symptoms, or worsening symptoms, and in combination with MRI results. “My interpretation of NfL is that it does have incremental value, telling us which patients have lesions that are more destructive, potentially, given all of these consistent associations with brain atrophy and disability progression over time,” said Dr. Sotirchos, who is an assistant professor of neurology at Johns Hopkins Medicine, Baltimore.

Dr. Abdelhak and Dr. Teunissen have no relevant financial disclosures. Dr. Sotirchos has financial relationships with Alexion, Viela Bio, Horizon Therapeutics, Genentech, and Ad Scientiam.

Neurofilament light chain (NfL) is a well-known and useful biomarker for multiple sclerosis (MS) disease activity, but its association with disease progression is not well understood. A new analysis of MS patients in California’s EPIC cohort suggests that NfL spikes occur about 1 year before clinical sign of MS disease worsening.

“We see evidence for accelerated neuroaxonal damage in the year preceding the first diagnosis of the progression events, [but] only if they were associated with evidence of focal inflammatory activity – that can be either clinical or imaging evidence,” said Ahmed Abdelhak, MD, during a presentation of the study at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

“By the time we diagnose the EDSS progression, it’s already too late. Every damage or any accelerated neuroaxonal damage that has happened in association with this event already took place around a year ago. I think [this has] huge implications for the designing of clinical trials,” said Dr. Abdelhak, who is a postdoctoral researcher at the University of California, San Francisco.

In the study, researchers analyzed data from 609 MS cases, with a total of 3,906 office visits. The median age was 42 years, and 69.6% were female. Median disease duration was 6 years.

They examined the association between NfL scores and confirmed disease worsening, as recorded by an increase in EDSS score. There was an increase in NfL age-adjusted z score about 12 months in advance among patients with a progression association with a relapse in the past year, compared with individuals who did not experience disease progression. There was also a more modest increase among individuals who had disease progression without a recent relapse, but this was not statistically significant.

“Our findings suggest that the association between NfL levels and EDSS worsening is most prominent in the setting of relapse-associated events,” said Dr. Abdelhak.
 

Clinical implications and audience skepticism

During the Q&A following the talk, session moderator Charlotte Teunissen, PhD, professor of neurochemistry at Amsterdam University Medical Center, asked about the clinical implication of the finding. “It seems that you concluded that axonal damage has been done before the progression starts. Is that your conclusion? So it means that there is no option to interfere anymore, consequently.”

Dr. Abdelhak responded: “I think that’s a very important interpretation of the data, which I’m sure is a relatively new way of thinking about it. That means, indeed, that when we see these patients, measuring NfL wouldn’t deliver any additional value because they don’t differ between the groups at the time of EDSS worsening. And there is probably nothing more we can do about this event. But it’s still very important to know that any therapeutic intervention has also the need to prevent future disability progression, future neuroaxonal damage, but regarding what has happened already, I’m a little bit skeptical if we will be able to change anything.”

Dr. Teunissen expressed skepticism that there was no further neurodegeneration following the spike in NfL, and pointed out an important caveat, which was the study’s reliance on NfL. “You base your conclusions on what you observe for NfL, and it’s a far-fetched conclusion that there is no further axonal damage ongoing. Maybe NfL is just one marker, and it’s not the best biomarker to measure progression,” she said.

Dr. Abdelhak conceded that it will be necessary to confirm the findings with other biomarkers of neurological injury. Even different subunits of the NfL protein have been shown to have different dynamics in other neurological conditions. “So the data we have give definitely an incomplete picture because we [know] nothing about the other biomarkers of neuroaxonal injury, including the other subunits of NfL,” he said.

Later in the Q&A, Alasdair Coles, MD, professor of neurology at University of Cambridge (England), spoke from the audience. He suggested that the findings could be seen as dispiriting for clinicians. “Would the panel agree that actually for a clinician this is all rather disappointing, because none of these markers are telling us anything that we don’t otherwise know by examining the patient and doing scans?”

“I can attempt to tackle that provocative question,” replied Elias Sotirchos, MD, who also presented on an association between NfL and brain atrophy research during the session. He pointed out that all clinical tests are imperfect, and suggested that NfL isn’t something to be used in isolation. It could be useful when patients are experiencing new symptoms, or worsening symptoms, and in combination with MRI results. “My interpretation of NfL is that it does have incremental value, telling us which patients have lesions that are more destructive, potentially, given all of these consistent associations with brain atrophy and disability progression over time,” said Dr. Sotirchos, who is an assistant professor of neurology at Johns Hopkins Medicine, Baltimore.

Dr. Abdelhak and Dr. Teunissen have no relevant financial disclosures. Dr. Sotirchos has financial relationships with Alexion, Viela Bio, Horizon Therapeutics, Genentech, and Ad Scientiam.

Circulating tumor DNA (ctDNA) has garnered attention in recent years as a potential noninvasive biomarker that could help determine prognosis and treatment responses in solid tumors. They could also provide a more complete picture of tumor genetics than the limited samples often available from a biopsy.

ctDNA studies have been conducted in a range of solid tumors, but esophageal cancer has received less attention than other cancers. It is currently diagnosed by endoscopy, but this method is not suitable for population-wide surveillance because of its cost and invasiveness.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type of esophageal cancer in China, and it is difficult to diagnose using normal radiological techniques because of the hollow nature of the esophagus.

In a virtual poster session at the annual meeting of the American Society for Radiation Oncology, Xin Wang, MD, discussed the results of a small study looking at ctDNA and ESCC. “We aimed to investigate if ctDNA could detect disease progression before radiological imaging and try identifying patients with inferior prognosis based on ctDNA positivity and dynamics,” said Dr. Wang, who is a researcher at the Chinese Academy of Medical Sciences, Beijing.

85% of enrolled patients were male, and the median age at diagnosis was 64 years. The gross tumor volume was larger in patients with ctDNA-positive tumors at baseline 40.1 cm³ versus 28.7 cm³ (P = .001) and 14% underwent esophagectomy following radiotherapy, compared with 58% of the ctDNA-negative group (P = .008). Other baseline factors were similar between the two groups.

The researchers used a 474-gene panel to analyze plasma samples. 106 of the genes are known to be associated with radiosensitivity. Prior to radiotherapy (T0), 28 of 40 patients (70%) had a positive ctDNA sample. At week 4 of radiotherapy (T1), 42% of 36 patients were ctDNA positive. One to 3 months after radiotherapy/chemoradiotherapy (T2), among 27 patients, 30% were ctDNA positive. 27 patients ultimately underwent esophagectomy, while 9 did not have surgery. Three to 6 months after radiotherapy/chemoradiotherapy (T3), among 23 patients, 22% were ctDNA positive. Of 14 patients alive after 1 year, 43% were ctDNA positive.

Over a median follow-up of 20.6 months, 17 patients were diagnosed with progression through radiological imaging. Of these, 13 patients (77%) were ctDNA positive before or after progression (Cohen’s kappa, 0.512; P < .01). The mean lead time was 5.5 months (95% confidence interval, 1.5-9.4 months).

The researchers also observed links between ctDNA and survival. “We observed a strong association between inferior progression-free survival [PFS] and ctDNA positivity at T1, T2, and T3 time points. Similar associations were detected in OS [overall survival] as well,” Dr. Wang said.

In a multivariate analysis, ctDNA positivity at T1 was associated worse PFS (hazard ratio, 3.35; 95% CI, 1.10-10.22), and there was a trend toward worse overall survival (HR, 2.48; 95% CI, 0.83-7.37). There were no statistically significant associations between ctDNA positivity and PFS or OS at T2.

Twenty-one patients experienced a decrease in ctDNA concentration between T0 and T1. Of these, eight patients achieved a clearance of ctDNA by T1, and they had a trend toward better PFS than patients who did not achieve clearance (HR, 0.31; P = .06).

“The relatively poor locoregional recurrence-free survival remains related to ctDNA positivity at T1. Interestingly, for ctDNA-negative patients who received surgery, none of them were diagnosed with radiological progression. To summarize, ctDNA is a promising biomarker for detecting disease progression. Positive ctDNA status indicates for PFS and OS, but patients achieving ctDNA clearance after radiation are likely to have a better PFS. There is also a potential association between ctDNA positivity at the fourth week during radiation therapy and higher risk of local recurrence, but further studies with a larger sample size are required,” Dr. Wang said.

Ann Raldow, MD, who served as a discussant following the poster presentation, pointed out that ctDNA has been found to be a useful prognostic and predictive tool in colon cancer. The new work suggests “that detectable ctDNA may help guide recommendations for postchemoradiation treatment. Of course, the ctDNA and esophageal cancer space is still in its infancy, and I would really encourage future studies to incorporate ctDNA as part of what they’re studying so that we can get more information about both the prognostic and predictive value of ctDNA in esophageal cancer,” said Dr. Raldow, who is an assistant professor of radiation oncology, University of California, Los Angeles.

Dr. Wang has no relevant financial disclosures. Dr. Raldow had received research funding from Intelligent Automation, Clarity, and Viewray.

Circulating tumor DNA (ctDNA) has garnered attention in recent years as a potential noninvasive biomarker that could help determine prognosis and treatment responses in solid tumors. They could also provide a more complete picture of tumor genetics than the limited samples often available from a biopsy.

ctDNA studies have been conducted in a range of solid tumors, but esophageal cancer has received less attention than other cancers. It is currently diagnosed by endoscopy, but this method is not suitable for population-wide surveillance because of its cost and invasiveness.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type of esophageal cancer in China, and it is difficult to diagnose using normal radiological techniques because of the hollow nature of the esophagus.

In a virtual poster session at the annual meeting of the American Society for Radiation Oncology, Xin Wang, MD, discussed the results of a small study looking at ctDNA and ESCC. “We aimed to investigate if ctDNA could detect disease progression before radiological imaging and try identifying patients with inferior prognosis based on ctDNA positivity and dynamics,” said Dr. Wang, who is a researcher at the Chinese Academy of Medical Sciences, Beijing.

85% of enrolled patients were male, and the median age at diagnosis was 64 years. The gross tumor volume was larger in patients with ctDNA-positive tumors at baseline 40.1 cm³ versus 28.7 cm³ (P = .001) and 14% underwent esophagectomy following radiotherapy, compared with 58% of the ctDNA-negative group (P = .008). Other baseline factors were similar between the two groups.

The researchers used a 474-gene panel to analyze plasma samples. 106 of the genes are known to be associated with radiosensitivity. Prior to radiotherapy (T0), 28 of 40 patients (70%) had a positive ctDNA sample. At week 4 of radiotherapy (T1), 42% of 36 patients were ctDNA positive. One to 3 months after radiotherapy/chemoradiotherapy (T2), among 27 patients, 30% were ctDNA positive. 27 patients ultimately underwent esophagectomy, while 9 did not have surgery. Three to 6 months after radiotherapy/chemoradiotherapy (T3), among 23 patients, 22% were ctDNA positive. Of 14 patients alive after 1 year, 43% were ctDNA positive.

Over a median follow-up of 20.6 months, 17 patients were diagnosed with progression through radiological imaging. Of these, 13 patients (77%) were ctDNA positive before or after progression (Cohen’s kappa, 0.512; P < .01). The mean lead time was 5.5 months (95% confidence interval, 1.5-9.4 months).

The researchers also observed links between ctDNA and survival. “We observed a strong association between inferior progression-free survival [PFS] and ctDNA positivity at T1, T2, and T3 time points. Similar associations were detected in OS [overall survival] as well,” Dr. Wang said.

In a multivariate analysis, ctDNA positivity at T1 was associated worse PFS (hazard ratio, 3.35; 95% CI, 1.10-10.22), and there was a trend toward worse overall survival (HR, 2.48; 95% CI, 0.83-7.37). There were no statistically significant associations between ctDNA positivity and PFS or OS at T2.

Twenty-one patients experienced a decrease in ctDNA concentration between T0 and T1. Of these, eight patients achieved a clearance of ctDNA by T1, and they had a trend toward better PFS than patients who did not achieve clearance (HR, 0.31; P = .06).

“The relatively poor locoregional recurrence-free survival remains related to ctDNA positivity at T1. Interestingly, for ctDNA-negative patients who received surgery, none of them were diagnosed with radiological progression. To summarize, ctDNA is a promising biomarker for detecting disease progression. Positive ctDNA status indicates for PFS and OS, but patients achieving ctDNA clearance after radiation are likely to have a better PFS. There is also a potential association between ctDNA positivity at the fourth week during radiation therapy and higher risk of local recurrence, but further studies with a larger sample size are required,” Dr. Wang said.

Ann Raldow, MD, who served as a discussant following the poster presentation, pointed out that ctDNA has been found to be a useful prognostic and predictive tool in colon cancer. The new work suggests “that detectable ctDNA may help guide recommendations for postchemoradiation treatment. Of course, the ctDNA and esophageal cancer space is still in its infancy, and I would really encourage future studies to incorporate ctDNA as part of what they’re studying so that we can get more information about both the prognostic and predictive value of ctDNA in esophageal cancer,” said Dr. Raldow, who is an assistant professor of radiation oncology, University of California, Los Angeles.

Dr. Wang has no relevant financial disclosures. Dr. Raldow had received research funding from Intelligent Automation, Clarity, and Viewray.

Circulating tumor DNA (ctDNA) has garnered attention in recent years as a potential noninvasive biomarker that could help determine prognosis and treatment responses in solid tumors. They could also provide a more complete picture of tumor genetics than the limited samples often available from a biopsy.

ctDNA studies have been conducted in a range of solid tumors, but esophageal cancer has received less attention than other cancers. It is currently diagnosed by endoscopy, but this method is not suitable for population-wide surveillance because of its cost and invasiveness.

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type of esophageal cancer in China, and it is difficult to diagnose using normal radiological techniques because of the hollow nature of the esophagus.

In a virtual poster session at the annual meeting of the American Society for Radiation Oncology, Xin Wang, MD, discussed the results of a small study looking at ctDNA and ESCC. “We aimed to investigate if ctDNA could detect disease progression before radiological imaging and try identifying patients with inferior prognosis based on ctDNA positivity and dynamics,” said Dr. Wang, who is a researcher at the Chinese Academy of Medical Sciences, Beijing.

85% of enrolled patients were male, and the median age at diagnosis was 64 years. The gross tumor volume was larger in patients with ctDNA-positive tumors at baseline 40.1 cm³ versus 28.7 cm³ (P = .001) and 14% underwent esophagectomy following radiotherapy, compared with 58% of the ctDNA-negative group (P = .008). Other baseline factors were similar between the two groups.

The researchers used a 474-gene panel to analyze plasma samples. 106 of the genes are known to be associated with radiosensitivity. Prior to radiotherapy (T0), 28 of 40 patients (70%) had a positive ctDNA sample. At week 4 of radiotherapy (T1), 42% of 36 patients were ctDNA positive. One to 3 months after radiotherapy/chemoradiotherapy (T2), among 27 patients, 30% were ctDNA positive. 27 patients ultimately underwent esophagectomy, while 9 did not have surgery. Three to 6 months after radiotherapy/chemoradiotherapy (T3), among 23 patients, 22% were ctDNA positive. Of 14 patients alive after 1 year, 43% were ctDNA positive.

Over a median follow-up of 20.6 months, 17 patients were diagnosed with progression through radiological imaging. Of these, 13 patients (77%) were ctDNA positive before or after progression (Cohen’s kappa, 0.512; P < .01). The mean lead time was 5.5 months (95% confidence interval, 1.5-9.4 months).

The researchers also observed links between ctDNA and survival. “We observed a strong association between inferior progression-free survival [PFS] and ctDNA positivity at T1, T2, and T3 time points. Similar associations were detected in OS [overall survival] as well,” Dr. Wang said.

In a multivariate analysis, ctDNA positivity at T1 was associated worse PFS (hazard ratio, 3.35; 95% CI, 1.10-10.22), and there was a trend toward worse overall survival (HR, 2.48; 95% CI, 0.83-7.37). There were no statistically significant associations between ctDNA positivity and PFS or OS at T2.

Twenty-one patients experienced a decrease in ctDNA concentration between T0 and T1. Of these, eight patients achieved a clearance of ctDNA by T1, and they had a trend toward better PFS than patients who did not achieve clearance (HR, 0.31; P = .06).

“The relatively poor locoregional recurrence-free survival remains related to ctDNA positivity at T1. Interestingly, for ctDNA-negative patients who received surgery, none of them were diagnosed with radiological progression. To summarize, ctDNA is a promising biomarker for detecting disease progression. Positive ctDNA status indicates for PFS and OS, but patients achieving ctDNA clearance after radiation are likely to have a better PFS. There is also a potential association between ctDNA positivity at the fourth week during radiation therapy and higher risk of local recurrence, but further studies with a larger sample size are required,” Dr. Wang said.

Ann Raldow, MD, who served as a discussant following the poster presentation, pointed out that ctDNA has been found to be a useful prognostic and predictive tool in colon cancer. The new work suggests “that detectable ctDNA may help guide recommendations for postchemoradiation treatment. Of course, the ctDNA and esophageal cancer space is still in its infancy, and I would really encourage future studies to incorporate ctDNA as part of what they’re studying so that we can get more information about both the prognostic and predictive value of ctDNA in esophageal cancer,” said Dr. Raldow, who is an assistant professor of radiation oncology, University of California, Los Angeles.

Dr. Wang has no relevant financial disclosures. Dr. Raldow had received research funding from Intelligent Automation, Clarity, and Viewray.

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

“This overall survival is greater than expected and impressive even in the era now of immunotherapy trials,” said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dr. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

“I think this is really one of the most important studies that’s come out in many years in terms of practice changing outcomes. We’ve seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there’s been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we’re really at a point where we can call this a standard of care for patients,” Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Dr. Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dr. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

“This overall survival is greater than expected and impressive even in the era now of immunotherapy trials,” said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dr. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

“I think this is really one of the most important studies that’s come out in many years in terms of practice changing outcomes. We’ve seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there’s been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we’re really at a point where we can call this a standard of care for patients,” Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Dr. Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dr. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

Among patients with advanced hepatocellular carcinoma (HCC), and especially those with macrovascular invasion, stereotactic body radiation therapy (SBRT) appears to grant a survival benefit when added to systemic therapy. That was the finding from a phase 3 clinical trial presented at the annual meeting of the American Society for Radiation Oncology.

For unresectable HCC or cases that cannot be treated with thermal ablation or regional therapy, the current standard of care is systemic therapy. When the study was conducted, the recommended therapy was the sorafenib, a tyrosine kinase inhibitor. But with the publication of the IMbrave 150 study in 2021, atezolizumab plus bevacizumab is now increasingly preferred by some oncologists.

In 2008, the SHARP study found that sorafenib improved median survival, but it provided less benefit for patients with macrovascular invasion. Various studies have addressed the question of whether radiation could improve survival among this patient population, but results have not been encouraging. Direct comparisons between sorafenib and radiotherapy in the SARAH and SIRveNIB studies showed no significant differences in outcomes.

To determine the efficacy of combined SBRT and sorafenib, researchers randomized 177 patients with locally advanced HCC to receive 400 mg sorafenib every 12 hours or SBRT of 27.5-50 Gy in five fractions, followed by 200 mg sorafenib every 12 hours for 4 weeks, then 400 mg sorafenib every 12 hours thereafter. The median age was 66 years, 85% of patients were male, 74% had macrovascular invasion. The study included patients with locally advanced tumors up to a 20-cm sum of diameters or up to a 20-cm conglomerate tumor, as well as those with metastases of 3 cm size or smaller.

After a median follow-up of 13.2 months, median overall survival was 15.8 months in the combination group, versus 12.3 months in sorafenib group (hazard ratio, 0.77; 1-sided P = .055). After a multivariable analysis, the combined treatment was associated with better overall survival (HR, 0.72; P = .042).

“This overall survival is greater than expected and impressive even in the era now of immunotherapy trials,” said Laura Dawson, MD, who presented the results of the study during a press conference at the meeting. Dr. Dawson is a professor of radiation oncology at University of Toronto and a radiation oncologist at Princess Margaret Hospital in Toronto.

Median progression-free survival was 9.2 months in the combined group versus 5.5 months in the sorafenib-only group (HR, 0.55; P = .0001). At 24 months, 17% of the combination group had 7% of the sorafenib group remained had not progressed. The median time to progression was 18.5 months in the combination group and 9.5 months in the sorafenib group (HR, 0.69; P = .034). The frequency of adverse events was similar in both groups. The study admitted patients with any level of vascular invasion, which contrasted with many earlier trials that excluded those with involvement of the main portal vein.

“I think this is really one of the most important studies that’s come out in many years in terms of practice changing outcomes. We’ve seen that with patients who have very high-risk HCC, especially patients who have portal vein or macrovascular vascular invasion, there’s been a significant improvement in overall survival for these patients, and this is a very difficult patient population. Adding SBRT in this group improved both the progression free survival and overall survival, so I think we’re really at a point where we can call this a standard of care for patients,” Karyn A. Goodman, MD, professor and vice chair of clinical research and radiation oncology at the Icahn School of Medicine at Mount Sinai, New York, said at the press conference.

A limitation of the study is that it closed early to accrual because of a change in the standard of care.

Dr. Goodman has served on advisory boards for Novartis, Philips Healthcare, and Genentech, and has consulted for RenovoRx and Syntactx. Dr. Dawson has received research grants from Merck and received patent/license fees or copyright compensation from RaySearch.

The effectiveness and safety of advanced therapies for psoriatic arthritis (PsA) was a focus of many published studies last month. Janus kinase inhibitors (JAKi) are a recent class of drugs made available to treat PsA and related diseases, and several clinical trials have been published. Sarabia and colleagues reported the results of a meta-analysis of 15 randomized controlled trials including 6757 patients with psoriasis or PsA who received treatment with a JAKi or placebo. Their analyses revealed that treatment with JAKi vs placebo was associated with higher odds of achieving American College of Rheumatology 20 (ACR20) response (odds ratio [OR] 4.45; 95% CI 3.64-5.44), with similar outcomes observed with tofacitinib vs placebo (OR 2.96; 95% CI 2.01-4.35) and non-tofacitinib JAKi vs placebo (OR 5.41; 95% CI 3.95-7.40). Serious adverse event rates were low (1%-7% in the maximum-dose intervention group).

Interleukin-23i (guselkumab, tildrakizumab, or risankizumab) are another class of biologics recently approved for the treatment of PsA. Preliminary results from a real-world study demonstrate the efficacy of these drugs for PsA. In a retrospective observational study including 80 patients with psoriasis (22 with PsA) who received guselkumab, tildrakizumab, or risankizumab, Elgaard and colleagues demonstrated that 40.9% or 36.4% of the PsA patients achieved complete or partial remission, respectively, compared with only 18.2% of patients with no improvement.

Regarding drug safety, a recent study demonstrated low rates of opportunistic infections with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARD (tsDMARD). Vassilopoulos and colleagues conducted a meta-analysis of 47 randomized controlled trials and 26 follow-up extension studies that included patients with PsA who received at least one dose of a bDMARD or a tsDMARD (n = 11,790) or placebo (n = 6425) during the placebo-controlled period, and 17,197 patients who received at least one dose of a bDMARD or a tsDMARD in the long-term extension period.

The cumulative incidence of opportunistic infections was < 3% when stratified by the mechanism of action: JAKi (2.72%; 95% CI 1.05%-5.04%), anti-interleukin (IL)-17i (1.18%; 95% CI 0.60%-1.90%), anti-IL-23i (0.24%; 95% CI 0.04%-0.54%), and TNFi (0.01%; 95% CI 0.00%-0.21%). These results are consistent with my own observations in my clinic. Thus, currently available advanced therapies, including JAKi and IL-23i, are effective and safe for the management of patients with PsA when used as monotherapy with or without conventional synthetic DMARD (csDMARD). Ongoing studies on combination therapy will provide us with guidance on the efficacy and safety of combining these drugs for the treatment of resistant disease.

Many patients do not respond to treatment, however. Actionable risk factors for lack of response are of clinical interest. One such factor is obesity. In an observational study of 774 adult PsA patients who started their first b/tsDMARD, Vallejo-Yague and colleagues reported that the odds of achieving minimal disease activity (adjusted OR [aOR] 0.45; 95% CI 0.24-0.82) and Disease Activity Index for Psoriatic Arthritis (DAPSA)-remission (aOR 0.42; 95% CI 0.21-0.85) were lower in the obese vs normal-weight group within the first year. Thus, obese patients had ~50% lower likelihood of achieving a state of low disease activity. Comprehensive management of PsA must include management of obesity and other comorbid conditions to achieve optimal outcomes.

Finally, an interesting study by Freuer and colleagues used bidirectional two-sample Mendelian randomization in 12,882 patients with inflammatory bowel disease (IBD), 21,770 matched controls, 5621 patients with psoriasis, 2063 patients with PsA, and 252,323 controls. The study found that genetically predicted IBD was associated with a higher risk for PsA (pooled OR 1.11; P = .003) with the risk being majorly mediated by Crohn's disease (OR 1.12; P = .002) and not ulcerative colitis (P = .70). Thus, patients with Crohn's disease need to be carefully evaluated for the development of PsA.

The effectiveness and safety of advanced therapies for psoriatic arthritis (PsA) was a focus of many published studies last month. Janus kinase inhibitors (JAKi) are a recent class of drugs made available to treat PsA and related diseases, and several clinical trials have been published. Sarabia and colleagues reported the results of a meta-analysis of 15 randomized controlled trials including 6757 patients with psoriasis or PsA who received treatment with a JAKi or placebo. Their analyses revealed that treatment with JAKi vs placebo was associated with higher odds of achieving American College of Rheumatology 20 (ACR20) response (odds ratio [OR] 4.45; 95% CI 3.64-5.44), with similar outcomes observed with tofacitinib vs placebo (OR 2.96; 95% CI 2.01-4.35) and non-tofacitinib JAKi vs placebo (OR 5.41; 95% CI 3.95-7.40). Serious adverse event rates were low (1%-7% in the maximum-dose intervention group).

Interleukin-23i (guselkumab, tildrakizumab, or risankizumab) are another class of biologics recently approved for the treatment of PsA. Preliminary results from a real-world study demonstrate the efficacy of these drugs for PsA. In a retrospective observational study including 80 patients with psoriasis (22 with PsA) who received guselkumab, tildrakizumab, or risankizumab, Elgaard and colleagues demonstrated that 40.9% or 36.4% of the PsA patients achieved complete or partial remission, respectively, compared with only 18.2% of patients with no improvement.

Regarding drug safety, a recent study demonstrated low rates of opportunistic infections with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARD (tsDMARD). Vassilopoulos and colleagues conducted a meta-analysis of 47 randomized controlled trials and 26 follow-up extension studies that included patients with PsA who received at least one dose of a bDMARD or a tsDMARD (n = 11,790) or placebo (n = 6425) during the placebo-controlled period, and 17,197 patients who received at least one dose of a bDMARD or a tsDMARD in the long-term extension period.

The cumulative incidence of opportunistic infections was < 3% when stratified by the mechanism of action: JAKi (2.72%; 95% CI 1.05%-5.04%), anti-interleukin (IL)-17i (1.18%; 95% CI 0.60%-1.90%), anti-IL-23i (0.24%; 95% CI 0.04%-0.54%), and TNFi (0.01%; 95% CI 0.00%-0.21%). These results are consistent with my own observations in my clinic. Thus, currently available advanced therapies, including JAKi and IL-23i, are effective and safe for the management of patients with PsA when used as monotherapy with or without conventional synthetic DMARD (csDMARD). Ongoing studies on combination therapy will provide us with guidance on the efficacy and safety of combining these drugs for the treatment of resistant disease.

Many patients do not respond to treatment, however. Actionable risk factors for lack of response are of clinical interest. One such factor is obesity. In an observational study of 774 adult PsA patients who started their first b/tsDMARD, Vallejo-Yague and colleagues reported that the odds of achieving minimal disease activity (adjusted OR [aOR] 0.45; 95% CI 0.24-0.82) and Disease Activity Index for Psoriatic Arthritis (DAPSA)-remission (aOR 0.42; 95% CI 0.21-0.85) were lower in the obese vs normal-weight group within the first year. Thus, obese patients had ~50% lower likelihood of achieving a state of low disease activity. Comprehensive management of PsA must include management of obesity and other comorbid conditions to achieve optimal outcomes.

Finally, an interesting study by Freuer and colleagues used bidirectional two-sample Mendelian randomization in 12,882 patients with inflammatory bowel disease (IBD), 21,770 matched controls, 5621 patients with psoriasis, 2063 patients with PsA, and 252,323 controls. The study found that genetically predicted IBD was associated with a higher risk for PsA (pooled OR 1.11; P = .003) with the risk being majorly mediated by Crohn's disease (OR 1.12; P = .002) and not ulcerative colitis (P = .70). Thus, patients with Crohn's disease need to be carefully evaluated for the development of PsA.

The effectiveness and safety of advanced therapies for psoriatic arthritis (PsA) was a focus of many published studies last month. Janus kinase inhibitors (JAKi) are a recent class of drugs made available to treat PsA and related diseases, and several clinical trials have been published. Sarabia and colleagues reported the results of a meta-analysis of 15 randomized controlled trials including 6757 patients with psoriasis or PsA who received treatment with a JAKi or placebo. Their analyses revealed that treatment with JAKi vs placebo was associated with higher odds of achieving American College of Rheumatology 20 (ACR20) response (odds ratio [OR] 4.45; 95% CI 3.64-5.44), with similar outcomes observed with tofacitinib vs placebo (OR 2.96; 95% CI 2.01-4.35) and non-tofacitinib JAKi vs placebo (OR 5.41; 95% CI 3.95-7.40). Serious adverse event rates were low (1%-7% in the maximum-dose intervention group).

Interleukin-23i (guselkumab, tildrakizumab, or risankizumab) are another class of biologics recently approved for the treatment of PsA. Preliminary results from a real-world study demonstrate the efficacy of these drugs for PsA. In a retrospective observational study including 80 patients with psoriasis (22 with PsA) who received guselkumab, tildrakizumab, or risankizumab, Elgaard and colleagues demonstrated that 40.9% or 36.4% of the PsA patients achieved complete or partial remission, respectively, compared with only 18.2% of patients with no improvement.

Regarding drug safety, a recent study demonstrated low rates of opportunistic infections with biologic disease-modifying antirheumatic drugs (bDMARD) and targeted synthetic DMARD (tsDMARD). Vassilopoulos and colleagues conducted a meta-analysis of 47 randomized controlled trials and 26 follow-up extension studies that included patients with PsA who received at least one dose of a bDMARD or a tsDMARD (n = 11,790) or placebo (n = 6425) during the placebo-controlled period, and 17,197 patients who received at least one dose of a bDMARD or a tsDMARD in the long-term extension period.

The cumulative incidence of opportunistic infections was < 3% when stratified by the mechanism of action: JAKi (2.72%; 95% CI 1.05%-5.04%), anti-interleukin (IL)-17i (1.18%; 95% CI 0.60%-1.90%), anti-IL-23i (0.24%; 95% CI 0.04%-0.54%), and TNFi (0.01%; 95% CI 0.00%-0.21%). These results are consistent with my own observations in my clinic. Thus, currently available advanced therapies, including JAKi and IL-23i, are effective and safe for the management of patients with PsA when used as monotherapy with or without conventional synthetic DMARD (csDMARD). Ongoing studies on combination therapy will provide us with guidance on the efficacy and safety of combining these drugs for the treatment of resistant disease.

Many patients do not respond to treatment, however. Actionable risk factors for lack of response are of clinical interest. One such factor is obesity. In an observational study of 774 adult PsA patients who started their first b/tsDMARD, Vallejo-Yague and colleagues reported that the odds of achieving minimal disease activity (adjusted OR [aOR] 0.45; 95% CI 0.24-0.82) and Disease Activity Index for Psoriatic Arthritis (DAPSA)-remission (aOR 0.42; 95% CI 0.21-0.85) were lower in the obese vs normal-weight group within the first year. Thus, obese patients had ~50% lower likelihood of achieving a state of low disease activity. Comprehensive management of PsA must include management of obesity and other comorbid conditions to achieve optimal outcomes.

Finally, an interesting study by Freuer and colleagues used bidirectional two-sample Mendelian randomization in 12,882 patients with inflammatory bowel disease (IBD), 21,770 matched controls, 5621 patients with psoriasis, 2063 patients with PsA, and 252,323 controls. The study found that genetically predicted IBD was associated with a higher risk for PsA (pooled OR 1.11; P = .003) with the risk being majorly mediated by Crohn's disease (OR 1.12; P = .002) and not ulcerative colitis (P = .70). Thus, patients with Crohn's disease need to be carefully evaluated for the development of PsA.

Agents proven to reduce major kidney issues in type 2 diabetes include renin-angiotensin system blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid inhibitors, but there are few data on the renal effects of the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. In a post-hoc analysis of the SURPASS-4 trial, Heerspink and colleagues reported that tirzepatide slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (ACR) compared with insulin glargine U100. There was also a reduction (≥ 40% decline) in the composite kidney outcome of eGFR, end-stage kidney disease (ESKD), death due to kidney failure, and new-onset macroalbuminuria, and this was driven by the reduction in new-onset macroalbuminuria. Although this was a post-hoc, exploratory analysis, the benefit of tirzepatide on kidney effects suggests that this agent should be studied in type 2 diabetes patients at high risk for kidney disease progression to determine whether indeed there will be a kidney protective effect.

Diabetes is the leading cause of ESKD, and recognizing patients at high risk for progression to ESKD is paramount. Abnormal glycolipid metabolism contributes to the development and progression of diabetic kidney disease (DKD). Bile acids, by regulating glycolipid metabolism, may indirectly provide renoprotective effects. Xiao and colleagues have published a retrospective cohort study of 184 Chinese patients with type 2 diabetes and biopsy-proven DKD. They found that low levels of bile acids (≤2.8 mmol/L) were associated with an over fivefold risk for ESKD after adjusting for known factors associated with ESKD. This is the first study suggesting a link between low bile acid levels and adverse kidney outcomes in DKD, and it provides a rationale for studying bile acid analogs as therapeutic agents for the treatment of DKD.

SGLT2 inhibitors and GLP-1 receptor agonists have proven cardiorenal benefits in type 2 diabetes, and each is recommended in guidelines for patients at higher risk for cardiorenal complications. There are no head-to-head randomized trials of SGLT2 inhibitors vs GLP-1 receptor agonists, and studies suggesting an increased risk for lower-extremity amputation with SGLT2 inhibitors have shown inconsistent results. Lee and colleagues conducted a retrospective cohort study in Taiwan, and, after propensity score-matching patients with type 2 diabetes treated with SGLT inhibitors or GLP-1 receptor agonists, they found no significant difference in major adverse limb events between the two groups. Although limited by retrospective design, short follow-up, and a low number of events, this study suggests that SGLT2 inhibitors and GLP-1 receptor agonists should continue to be used as indicated and according to diabetes guidelines, with no difference in amputation rates between these two classes of antihyperglycemic agents.

Gastrointestinal adverse events are the most common side effects related to metformin use. Many clinicians choose an extended-release metformin preparation over immediate-release, believing that there may be better tolerability, but studies have shown inconsistent results. In a systematic review, meta-analysis, and meta-regression of randomized controlled trials, Nabrdalik and colleagues demonstrated an increased risk for abdominal pain, nausea, and diarrhea with metformin compared with other antidiabetic drugs or placebo, as well as a reduced risk for bloating and diarrhea with extended-release metformin compared with immediate-release formulations. These findings reinforce the practice for considering metformin extended-release over immediate-release formulations to reduce the chance of gastrointestinal side effects.

Agents proven to reduce major kidney issues in type 2 diabetes include renin-angiotensin system blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid inhibitors, but there are few data on the renal effects of the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. In a post-hoc analysis of the SURPASS-4 trial, Heerspink and colleagues reported that tirzepatide slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (ACR) compared with insulin glargine U100. There was also a reduction (≥ 40% decline) in the composite kidney outcome of eGFR, end-stage kidney disease (ESKD), death due to kidney failure, and new-onset macroalbuminuria, and this was driven by the reduction in new-onset macroalbuminuria. Although this was a post-hoc, exploratory analysis, the benefit of tirzepatide on kidney effects suggests that this agent should be studied in type 2 diabetes patients at high risk for kidney disease progression to determine whether indeed there will be a kidney protective effect.

Diabetes is the leading cause of ESKD, and recognizing patients at high risk for progression to ESKD is paramount. Abnormal glycolipid metabolism contributes to the development and progression of diabetic kidney disease (DKD). Bile acids, by regulating glycolipid metabolism, may indirectly provide renoprotective effects. Xiao and colleagues have published a retrospective cohort study of 184 Chinese patients with type 2 diabetes and biopsy-proven DKD. They found that low levels of bile acids (≤2.8 mmol/L) were associated with an over fivefold risk for ESKD after adjusting for known factors associated with ESKD. This is the first study suggesting a link between low bile acid levels and adverse kidney outcomes in DKD, and it provides a rationale for studying bile acid analogs as therapeutic agents for the treatment of DKD.

SGLT2 inhibitors and GLP-1 receptor agonists have proven cardiorenal benefits in type 2 diabetes, and each is recommended in guidelines for patients at higher risk for cardiorenal complications. There are no head-to-head randomized trials of SGLT2 inhibitors vs GLP-1 receptor agonists, and studies suggesting an increased risk for lower-extremity amputation with SGLT2 inhibitors have shown inconsistent results. Lee and colleagues conducted a retrospective cohort study in Taiwan, and, after propensity score-matching patients with type 2 diabetes treated with SGLT inhibitors or GLP-1 receptor agonists, they found no significant difference in major adverse limb events between the two groups. Although limited by retrospective design, short follow-up, and a low number of events, this study suggests that SGLT2 inhibitors and GLP-1 receptor agonists should continue to be used as indicated and according to diabetes guidelines, with no difference in amputation rates between these two classes of antihyperglycemic agents.

Gastrointestinal adverse events are the most common side effects related to metformin use. Many clinicians choose an extended-release metformin preparation over immediate-release, believing that there may be better tolerability, but studies have shown inconsistent results. In a systematic review, meta-analysis, and meta-regression of randomized controlled trials, Nabrdalik and colleagues demonstrated an increased risk for abdominal pain, nausea, and diarrhea with metformin compared with other antidiabetic drugs or placebo, as well as a reduced risk for bloating and diarrhea with extended-release metformin compared with immediate-release formulations. These findings reinforce the practice for considering metformin extended-release over immediate-release formulations to reduce the chance of gastrointestinal side effects.

Agents proven to reduce major kidney issues in type 2 diabetes include renin-angiotensin system blockers, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid inhibitors, but there are few data on the renal effects of the glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide. In a post-hoc analysis of the SURPASS-4 trial, Heerspink and colleagues reported that tirzepatide slowed the rate of estimated glomerular filtration rate (eGFR) decline and reduced urine albumin-to-creatinine ratio (ACR) compared with insulin glargine U100. There was also a reduction (≥ 40% decline) in the composite kidney outcome of eGFR, end-stage kidney disease (ESKD), death due to kidney failure, and new-onset macroalbuminuria, and this was driven by the reduction in new-onset macroalbuminuria. Although this was a post-hoc, exploratory analysis, the benefit of tirzepatide on kidney effects suggests that this agent should be studied in type 2 diabetes patients at high risk for kidney disease progression to determine whether indeed there will be a kidney protective effect.

Diabetes is the leading cause of ESKD, and recognizing patients at high risk for progression to ESKD is paramount. Abnormal glycolipid metabolism contributes to the development and progression of diabetic kidney disease (DKD). Bile acids, by regulating glycolipid metabolism, may indirectly provide renoprotective effects. Xiao and colleagues have published a retrospective cohort study of 184 Chinese patients with type 2 diabetes and biopsy-proven DKD. They found that low levels of bile acids (≤2.8 mmol/L) were associated with an over fivefold risk for ESKD after adjusting for known factors associated with ESKD. This is the first study suggesting a link between low bile acid levels and adverse kidney outcomes in DKD, and it provides a rationale for studying bile acid analogs as therapeutic agents for the treatment of DKD.

SGLT2 inhibitors and GLP-1 receptor agonists have proven cardiorenal benefits in type 2 diabetes, and each is recommended in guidelines for patients at higher risk for cardiorenal complications. There are no head-to-head randomized trials of SGLT2 inhibitors vs GLP-1 receptor agonists, and studies suggesting an increased risk for lower-extremity amputation with SGLT2 inhibitors have shown inconsistent results. Lee and colleagues conducted a retrospective cohort study in Taiwan, and, after propensity score-matching patients with type 2 diabetes treated with SGLT inhibitors or GLP-1 receptor agonists, they found no significant difference in major adverse limb events between the two groups. Although limited by retrospective design, short follow-up, and a low number of events, this study suggests that SGLT2 inhibitors and GLP-1 receptor agonists should continue to be used as indicated and according to diabetes guidelines, with no difference in amputation rates between these two classes of antihyperglycemic agents.

Gastrointestinal adverse events are the most common side effects related to metformin use. Many clinicians choose an extended-release metformin preparation over immediate-release, believing that there may be better tolerability, but studies have shown inconsistent results. In a systematic review, meta-analysis, and meta-regression of randomized controlled trials, Nabrdalik and colleagues demonstrated an increased risk for abdominal pain, nausea, and diarrhea with metformin compared with other antidiabetic drugs or placebo, as well as a reduced risk for bloating and diarrhea with extended-release metformin compared with immediate-release formulations. These findings reinforce the practice for considering metformin extended-release over immediate-release formulations to reduce the chance of gastrointestinal side effects.

Richards and colleagues explored the effects of aspirin prophylaxis in women with chronic hypertension. They did not detect a lowered risk for preeclampsia but did note a significantly decreased risk for preterm birth in the aspirin group. This was a systematic review and meta-analysis of nine studies (including retrospective cohort and randomized controlled trials). The mixed quality of the source data did limit the meta-analysis. However, this finding suggests that further research is warranted, and we may have a new role for aspirin in helping to decrease preterm birth in women with chronic hypertension.

Cleary and colleagues investigated the use of 30 mg oral nifedipine ER given every 24 hours until delivery in patients with preE with SF. In this randomized, triple-blinded, placebo-controlled trial, 110 patients were randomly assigned to nifedipine treatment or placebo. The results suggest a role for this medication early in the treatment of preE with SF, as the treated patients were much less likely to require acute therapy for severe-range blood pressure. The researchers also noted a trend toward fewer cesarean deliveries (20.8% vs 34.7%) and lower neonatal intensive care unit admissions (29.1% vs 47.1%) in the nifedipine ER group. This favors the use of nifedipine ER in patients with preE with SF.

Stewart and colleagues examined the more common morbidities associated with MTOP after 20 weeks estimated gestational age using a 10-year retrospective cohort study involving 407 patients. They found that 99% of the women had a successful vaginal delivery; however, 25% had some morbidity. Additionally, 16% of the women needed manual removal of placental tissue, 11% had postpartum hemorrhage, and 1.3% experienced severe maternal morbidity (including amniotic fluid embolism), but no maternal deaths occurred. Increased surveillance for postpartum hemorrhage in this patient population should be considered.

Righini and colleagues provide reassurance regarding a commonly used test to rule out pulmonary embolism in pregnant women. They present ancillary data from a prospective management outcome study of 149 women who underwent CT pulmonary angiography testing in pregnancy. There have been concerns raised regarding potential harmful effects related to intravenous iodinated contrast agents on thyroid function. None of the infants born to these patients had evidence of neonatal hypothyroidism (assessed via thyroid-stimulating hormone measurements). This gives reassurance that the use of CT pulmonary angiography testing for pulmonary embolism in pregnancy is safe.

Richards and colleagues explored the effects of aspirin prophylaxis in women with chronic hypertension. They did not detect a lowered risk for preeclampsia but did note a significantly decreased risk for preterm birth in the aspirin group. This was a systematic review and meta-analysis of nine studies (including retrospective cohort and randomized controlled trials). The mixed quality of the source data did limit the meta-analysis. However, this finding suggests that further research is warranted, and we may have a new role for aspirin in helping to decrease preterm birth in women with chronic hypertension.

Cleary and colleagues investigated the use of 30 mg oral nifedipine ER given every 24 hours until delivery in patients with preE with SF. In this randomized, triple-blinded, placebo-controlled trial, 110 patients were randomly assigned to nifedipine treatment or placebo. The results suggest a role for this medication early in the treatment of preE with SF, as the treated patients were much less likely to require acute therapy for severe-range blood pressure. The researchers also noted a trend toward fewer cesarean deliveries (20.8% vs 34.7%) and lower neonatal intensive care unit admissions (29.1% vs 47.1%) in the nifedipine ER group. This favors the use of nifedipine ER in patients with preE with SF.

Stewart and colleagues examined the more common morbidities associated with MTOP after 20 weeks estimated gestational age using a 10-year retrospective cohort study involving 407 patients. They found that 99% of the women had a successful vaginal delivery; however, 25% had some morbidity. Additionally, 16% of the women needed manual removal of placental tissue, 11% had postpartum hemorrhage, and 1.3% experienced severe maternal morbidity (including amniotic fluid embolism), but no maternal deaths occurred. Increased surveillance for postpartum hemorrhage in this patient population should be considered.

Righini and colleagues provide reassurance regarding a commonly used test to rule out pulmonary embolism in pregnant women. They present ancillary data from a prospective management outcome study of 149 women who underwent CT pulmonary angiography testing in pregnancy. There have been concerns raised regarding potential harmful effects related to intravenous iodinated contrast agents on thyroid function. None of the infants born to these patients had evidence of neonatal hypothyroidism (assessed via thyroid-stimulating hormone measurements). This gives reassurance that the use of CT pulmonary angiography testing for pulmonary embolism in pregnancy is safe.

Richards and colleagues explored the effects of aspirin prophylaxis in women with chronic hypertension. They did not detect a lowered risk for preeclampsia but did note a significantly decreased risk for preterm birth in the aspirin group. This was a systematic review and meta-analysis of nine studies (including retrospective cohort and randomized controlled trials). The mixed quality of the source data did limit the meta-analysis. However, this finding suggests that further research is warranted, and we may have a new role for aspirin in helping to decrease preterm birth in women with chronic hypertension.

Cleary and colleagues investigated the use of 30 mg oral nifedipine ER given every 24 hours until delivery in patients with preE with SF. In this randomized, triple-blinded, placebo-controlled trial, 110 patients were randomly assigned to nifedipine treatment or placebo. The results suggest a role for this medication early in the treatment of preE with SF, as the treated patients were much less likely to require acute therapy for severe-range blood pressure. The researchers also noted a trend toward fewer cesarean deliveries (20.8% vs 34.7%) and lower neonatal intensive care unit admissions (29.1% vs 47.1%) in the nifedipine ER group. This favors the use of nifedipine ER in patients with preE with SF.

Stewart and colleagues examined the more common morbidities associated with MTOP after 20 weeks estimated gestational age using a 10-year retrospective cohort study involving 407 patients. They found that 99% of the women had a successful vaginal delivery; however, 25% had some morbidity. Additionally, 16% of the women needed manual removal of placental tissue, 11% had postpartum hemorrhage, and 1.3% experienced severe maternal morbidity (including amniotic fluid embolism), but no maternal deaths occurred. Increased surveillance for postpartum hemorrhage in this patient population should be considered.

Righini and colleagues provide reassurance regarding a commonly used test to rule out pulmonary embolism in pregnant women. They present ancillary data from a prospective management outcome study of 149 women who underwent CT pulmonary angiography testing in pregnancy. There have been concerns raised regarding potential harmful effects related to intravenous iodinated contrast agents on thyroid function. None of the infants born to these patients had evidence of neonatal hypothyroidism (assessed via thyroid-stimulating hormone measurements). This gives reassurance that the use of CT pulmonary angiography testing for pulmonary embolism in pregnancy is safe.

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

A total of 126 patients were included in the full analysis set; median progression-free survival (PFS) was 18.8 months, overall response rate was 64.3%, and the safety profile was similar to prior studies. The median PFS in this observational study was comparable to a median PFS of 16.9 months in the CLEOPTRA study among 88 patients with prior (neo)adjuvant trastuzumab. HELENA also demonstrated similar PFS results for the hormone receptor (HR)-negative and HR-positive (HR+) subgroups (19.4 months vs 18.2 months), as well as for patients with nonvisceral and visceral metastases (20.5 months vs 18.0 months). These findings provide further support for use of the THP regimen as first-line treatment in the real-world setting for patients with HER2+ MBC and prior receipt of trastuzumab.

Adjuvant endocrine therapy (ET) is associated with a survival benefit for early-stage HR+ breast cancer; however, the absolute degree of benefit depends on various clinicopathologic features.² Although it generally has a manageable toxicity profile, some side effects carry more significant consequences (thromboembolism, endometrial carcinoma, osteoporosis), and some of the more common ones can affect routine quality of life (hot flashes, vaginal dryness, arthralgia).

A retrospective observational study including 5545 patients with pT1a-b estrogen receptor-positive (ER+) breast cancer demonstrated improvements in disease-free survival (DFS) and recurrence-free survival (RFS) among those who received ET vs those who did not receive ET after 5 and 7 years of follow-up (DFS: increases of 2.5% and 3.3%; RFS: increases of 1.9% and 4.3%) (Houvenaeghel et al). Among all patients, absence of ET was associated with decreased DFS (hazard ratio [HR] 1.275; P = .047) but no difference in RFS or OS. Patients with pT1a-b ER+ grade 2-3 tumors (n = 2363) experienced decreased DFS (HR 1.502, P = .049) without ET; however, those with pT1a-b ER+ grade 1 tumors did not experience a negative effect on DFS without ET.

These results provide further support for the survival improvements seen with adjuvant ET — although the relative benefit may be fairly modest — and that ET omission is a relevant consideration in patients with comorbidities or tolerance issues, particularly those with pT1a-b grade 1 tumors.

Advancements in breast cancer therapies have led to improvements in survival outcomes, and it is therefore increasingly essential to recognize risks for other cancer types in breast cancer survivors. Male breast cancer is rare, and although clinical management for the most part mirrors that of female breast cancer, it is important to be aware of potential differences in this population, including risks for subsequent non-breast primary cancers.³

A meta-analysis including eight retrospective cohort studies with male breast cancer survivors reported the standardized incidence ratio (SIR), which compares the incidence of non-breast second primary cancers (SPC) among men with first primary breast cancer vs the expected incidence of non-breast primary cancers in the general male population. The summary SIR estimate was 1.27 (95% CI 1.03-1.56), with increased risk for certain SPCs: colorectal (SIR 1.29; 95% CI 1.03-1.61), pancreatic (SIR 1.64; 95% CI 1.05-2.55), and thyroid (SIR 5.58; 95% CI 1.04-30.05) (Allen et al). Additionally, men diagnosed with breast cancer before 50 years of age were observed to have increased SPC risk compared with men who were older than 50 years at breast cancer onset (SIR 1.50 vs 1.14; P = .040).

This study highlights the importance of genetic assessment for men diagnosed with breast cancer, so they can be appropriately counseled on subsequent cancer risk. It also stimulates thinking regarding other potential contributing factors to the observed increased SPC risk among male breast cancer survivors, including the effect of various treatments, hormonal influences, and significant family history.

Studies have shown that older women derive a survival benefit with adjuvant chemotherapy; however, they may be at increased risk of experiencing toxicities owing to physical functioning and comorbidities.⁴ A comprehensive geriatric assessment is key, and it is also beneficial for identifying which patients have a higher likelihood of clinical decline after chemotherapy.

A prospective study including 295 robust women age ≥ 65 years with stage I-III breast cancer treated with chemotherapy showed that 26% had a chemotherapy-induced decline in frailty status; patients with high interleukin-6 (IL-6) and C-reactive protein (CRP) inflammatory markers before chemotherapy had a more than threefold odds of experiencing a chemotherapy-induced decline in frailty compared with those with low IL-6 and CRP (odds ratio 3.52; 95% CI 1.55-8.01; P = .003) (Ji et al).

These findings support the relationship between inflammation, aging, and chemotherapy-induced functional decline. Further research is warranted to identify whether there are specific drugs that are implicated, methods to enhance anti-inflammatory effects, and any downstream effect on breast cancer outcomes of these patients.

Additional References

1. Swain SM, Miles D, Kim SB, et al; CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): End-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
2. Ma SJ, Oladeru OT, Singh AK. Association of endocrine therapy with overall survival in women with small, hormone receptor-positive, ERBB2-negative breast cancer. JAMA Netw Open. 2020;3:e2013973. Doi: 10.1001/jamanetworkopen.2020.13973
3. Pritzlaff M, Summerour P, McFarland R, et al. Male breast cancer in a multi-gene panel testing cohort: Insights and unexpected results. Breast Cancer Res Treat. 2017;161:575-586. Doi: 10.1007/s10549-016-4085-4
4. Tamirisa N, Lin H, Shen Y, et al. Association of chemotherapy with survival in elderly patients with multiple comorbidities and estrogen receptor-positive, node-positive breast cancer. JAMA Oncol. 2020;6:1548-155 Doi: 10.1001/jamaoncol.2020.2388

Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.

Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.

Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.

For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.

Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.

Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.

Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.

For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.

Still, some patients seek alternative or adjunctive treatment approaches, owing to a desire to identify the root cause of disease, their aversion toward Western medicine, or fear of adverse events. Yepes-Nuñez and colleagues performed a systematic review and meta-analysis including 23 studies of benefits and harms of allergen immunotherapy for AD. I had the privilege of participating in this study and can testify to the astronomical amount of work that went into comprehensively identifying all of the relevant studies and synthesizing the data. We found that adjunctive subcutaneous or sublingual allergen immunotherapy, particularly for house dust mites, led to modest but generally delayed improvements of AD severity, itch, and quality of life, and less definitive effects on sleep disturbance and AD flares. Overall, both were well tolerated, though subcutaneous immunotherapy was associated with more adverse events than sublingual immunotherapy. Allergen immunotherapy requires a significant investment of time by patients and was only modestly effective. Nevertheless, it may be a reasonable approach to consider in select patients with AD.

Benjamin Franklin famously stated that "an ounce of prevention is worth a pound of cure." Likewise, while successful treatment of AD is great, how can we advise patients and caregivers of children who are at high risk for AD? To answer this question, Voigt and Lele performed a systematic review and meta-analysis of 11 randomized controlled trials examining the efficacy of Lactobacillus rhamnosus at preventing AD in children when taken by mothers during pregnancy. They found that L. rhamnosus significantly reduced the risk of developing AD within 2 years, marginally significantly reduced risk at 4-5 years, and significantly reduced risk at 6-7 years, but no significant risk differences were observed at 10-11 years. The authors concluded that use of L. rhamnosus with or without other probiotics during pregnancy reduces the incidence of childhood AD at least up to age 7 years.

Wang and colleagues conducted an observational study of the relationship of home environment exposures with atopic disease, including AD, in 17,881 offspring from Iceland, Norway, Sweden, Denmark, and Estonia who had undergone two follow-up investigations every 10 years. They found that AD was associated with parent-reported visible mold and dampness/mold at home, living in an apartment, and living in newer buildings. Avoidance of these environmental exposures could possibly decrease the risk of developing AD, although future confirmatory studies are needed.

For each of these treatment/prevention approaches, the magnitude of benefit is not very large. Thus, these approaches do not replace our armamentarium of treatments and avoidance strategies for AD. Rather, they can be used complementarily as low-risk add-on interventions with a potential upside.

Heart failure (HF) patients with high serum levels of alpha-linolenic acid (ALA) had a better prognosis than those with the lowest levels, in an observational study.

ALA is an omega-3 fatty acid that is found mainly in plants, including flaxseed, chia, walnuts, or canola oil.

PxHere

Plant power

Dr. Sala-Vila and colleagues analyzed data and samples from 905 patients (mean age, 67; 32% women) with HF of different etiologies. ALA was assessed by gas chromatography in serum phospholipids, which reflect long-term dietary ALA intake and metabolism.

The primary outcome was a composite of all-cause death or first HF hospitalization. The secondary outcome was the composite of CV death or HF hospitalization.

After a median follow-up of 2.4 years, 140 all-cause deaths, 85 CV deaths, and 141 first HF hospitalizations occurred (composite of all-cause death and first HF hospitalization, 238; composite of CV death and HF hospitalization, 184).

Compared with patients at the lowest quartile of ALA in serum phospholipids, those at the three upper quartiles showed a 39% reduction in the risk of the primary endpoint (hazard ratio, 0.61).

Statistically significant reductions also were observed for all-cause death (HR, 0.58), CV death (HR, 0.51), first HF hospitalization (HR, 0.58), and the composite of CV death and HF hospitalization (HR, 0.58).

By contrast, nonstatistically significant associations were seen for fish-derived EPA, DHA, and the sum of EPA + DHA.

Limitations of the study include its observational nature; a relatively young cohort with reduced or mid-range ejection fraction and stage 2 chronic kidney disease; and no dietary data except for those regarding fatty acids.

“Controversial results from landmark recent trials on omega-3 might have translated into confusion/negative impact on the reputation of these fatty acids,” Dr. Sala-Vila noted. “Many factors affect how each participant responds to a certain intervention (precision nutrition), such as genetics, the microbiome, and the environment. In this regard, nutritional status – omega-3 background – is emerging as a key determinant.”
 

Randomized trials needed

JoAnn E. Manson, MD, MPH, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Boston, said the findings “are promising in the context of earlier research on omega-3s.”

Those studies include the landmark GISSI-HF trial, a randomized, controlled trial (RCT) that showed a small benefit of n-3 polyunsaturated fatty acids regarding hospital admissions and mortality among patients with chronic HF, and her team’s VITAL-HF study, which showed a significant reduction in recurrent HF hospitalization with marine omega-3 supplementation versus placebo.

“This may not be a causal association, and the authors acknowledge that they don’t have information on other dietary factors,” Dr. Manson said. “It may be that the foods that are leading to this higher blood level of ALA comprise the type of plant-based diet that’s been linked to lower risk of CVD, such as the Mediterranean diet. The findings also could be the result of other factors that aren’t fully controlled for in the analysis, or the participants could be more compliant with their medications.”

Nevertheless, she said, “it’s reasonable to recommend that people with a history of HF or who are at high risk of HF increase their intake of ALA-enriched foods, including canola oil, flaxseed oils, soybeans and soybean oils, and walnuts.”

“I think the evidence is promising enough that an RCT of ALA in people with heart failure also would be reasonable,” she added.

Similarly, Abdallah Al-Mohammad, MD, of Northern General Hospital, Sheffield, England, writes in a related editorial that while a potential role for ALA in improving morbidity and mortality in HF patients cannot be substantiated yet, the findings “open the field to more questions” for which “the judge and jury ... shall be prospective randomized controlled trials.”

No commercial funding or relevant conflicts of interest were declared.

A version of this article first appeared on Medscape.com.

Heart failure (HF) patients with high serum levels of alpha-linolenic acid (ALA) had a better prognosis than those with the lowest levels, in an observational study.

ALA is an omega-3 fatty acid that is found mainly in plants, including flaxseed, chia, walnuts, or canola oil.

PxHere

Plant power

Dr. Sala-Vila and colleagues analyzed data and samples from 905 patients (mean age, 67; 32% women) with HF of different etiologies. ALA was assessed by gas chromatography in serum phospholipids, which reflect long-term dietary ALA intake and metabolism.

The primary outcome was a composite of all-cause death or first HF hospitalization. The secondary outcome was the composite of CV death or HF hospitalization.

After a median follow-up of 2.4 years, 140 all-cause deaths, 85 CV deaths, and 141 first HF hospitalizations occurred (composite of all-cause death and first HF hospitalization, 238; composite of CV death and HF hospitalization, 184).

Compared with patients at the lowest quartile of ALA in serum phospholipids, those at the three upper quartiles showed a 39% reduction in the risk of the primary endpoint (hazard ratio, 0.61).

Statistically significant reductions also were observed for all-cause death (HR, 0.58), CV death (HR, 0.51), first HF hospitalization (HR, 0.58), and the composite of CV death and HF hospitalization (HR, 0.58).

By contrast, nonstatistically significant associations were seen for fish-derived EPA, DHA, and the sum of EPA + DHA.

Limitations of the study include its observational nature; a relatively young cohort with reduced or mid-range ejection fraction and stage 2 chronic kidney disease; and no dietary data except for those regarding fatty acids.

“Controversial results from landmark recent trials on omega-3 might have translated into confusion/negative impact on the reputation of these fatty acids,” Dr. Sala-Vila noted. “Many factors affect how each participant responds to a certain intervention (precision nutrition), such as genetics, the microbiome, and the environment. In this regard, nutritional status – omega-3 background – is emerging as a key determinant.”
 

Randomized trials needed

JoAnn E. Manson, MD, MPH, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Boston, said the findings “are promising in the context of earlier research on omega-3s.”

Those studies include the landmark GISSI-HF trial, a randomized, controlled trial (RCT) that showed a small benefit of n-3 polyunsaturated fatty acids regarding hospital admissions and mortality among patients with chronic HF, and her team’s VITAL-HF study, which showed a significant reduction in recurrent HF hospitalization with marine omega-3 supplementation versus placebo.

“This may not be a causal association, and the authors acknowledge that they don’t have information on other dietary factors,” Dr. Manson said. “It may be that the foods that are leading to this higher blood level of ALA comprise the type of plant-based diet that’s been linked to lower risk of CVD, such as the Mediterranean diet. The findings also could be the result of other factors that aren’t fully controlled for in the analysis, or the participants could be more compliant with their medications.”

Nevertheless, she said, “it’s reasonable to recommend that people with a history of HF or who are at high risk of HF increase their intake of ALA-enriched foods, including canola oil, flaxseed oils, soybeans and soybean oils, and walnuts.”

“I think the evidence is promising enough that an RCT of ALA in people with heart failure also would be reasonable,” she added.

Similarly, Abdallah Al-Mohammad, MD, of Northern General Hospital, Sheffield, England, writes in a related editorial that while a potential role for ALA in improving morbidity and mortality in HF patients cannot be substantiated yet, the findings “open the field to more questions” for which “the judge and jury ... shall be prospective randomized controlled trials.”

No commercial funding or relevant conflicts of interest were declared.

A version of this article first appeared on Medscape.com.

Heart failure (HF) patients with high serum levels of alpha-linolenic acid (ALA) had a better prognosis than those with the lowest levels, in an observational study.

ALA is an omega-3 fatty acid that is found mainly in plants, including flaxseed, chia, walnuts, or canola oil.

PxHere

Plant power

Dr. Sala-Vila and colleagues analyzed data and samples from 905 patients (mean age, 67; 32% women) with HF of different etiologies. ALA was assessed by gas chromatography in serum phospholipids, which reflect long-term dietary ALA intake and metabolism.

The primary outcome was a composite of all-cause death or first HF hospitalization. The secondary outcome was the composite of CV death or HF hospitalization.

After a median follow-up of 2.4 years, 140 all-cause deaths, 85 CV deaths, and 141 first HF hospitalizations occurred (composite of all-cause death and first HF hospitalization, 238; composite of CV death and HF hospitalization, 184).

Compared with patients at the lowest quartile of ALA in serum phospholipids, those at the three upper quartiles showed a 39% reduction in the risk of the primary endpoint (hazard ratio, 0.61).

Statistically significant reductions also were observed for all-cause death (HR, 0.58), CV death (HR, 0.51), first HF hospitalization (HR, 0.58), and the composite of CV death and HF hospitalization (HR, 0.58).

By contrast, nonstatistically significant associations were seen for fish-derived EPA, DHA, and the sum of EPA + DHA.

Limitations of the study include its observational nature; a relatively young cohort with reduced or mid-range ejection fraction and stage 2 chronic kidney disease; and no dietary data except for those regarding fatty acids.

“Controversial results from landmark recent trials on omega-3 might have translated into confusion/negative impact on the reputation of these fatty acids,” Dr. Sala-Vila noted. “Many factors affect how each participant responds to a certain intervention (precision nutrition), such as genetics, the microbiome, and the environment. In this regard, nutritional status – omega-3 background – is emerging as a key determinant.”
 

Randomized trials needed

JoAnn E. Manson, MD, MPH, DrPH, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital, Boston, said the findings “are promising in the context of earlier research on omega-3s.”

Those studies include the landmark GISSI-HF trial, a randomized, controlled trial (RCT) that showed a small benefit of n-3 polyunsaturated fatty acids regarding hospital admissions and mortality among patients with chronic HF, and her team’s VITAL-HF study, which showed a significant reduction in recurrent HF hospitalization with marine omega-3 supplementation versus placebo.

“This may not be a causal association, and the authors acknowledge that they don’t have information on other dietary factors,” Dr. Manson said. “It may be that the foods that are leading to this higher blood level of ALA comprise the type of plant-based diet that’s been linked to lower risk of CVD, such as the Mediterranean diet. The findings also could be the result of other factors that aren’t fully controlled for in the analysis, or the participants could be more compliant with their medications.”

Nevertheless, she said, “it’s reasonable to recommend that people with a history of HF or who are at high risk of HF increase their intake of ALA-enriched foods, including canola oil, flaxseed oils, soybeans and soybean oils, and walnuts.”

“I think the evidence is promising enough that an RCT of ALA in people with heart failure also would be reasonable,” she added.

Similarly, Abdallah Al-Mohammad, MD, of Northern General Hospital, Sheffield, England, writes in a related editorial that while a potential role for ALA in improving morbidity and mortality in HF patients cannot be substantiated yet, the findings “open the field to more questions” for which “the judge and jury ... shall be prospective randomized controlled trials.”

No commercial funding or relevant conflicts of interest were declared.

A version of this article first appeared on Medscape.com.