Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

Exposure to air pollution may contribute to significant reductions in life expectancy in the United States, particularly among lower-income populations, research suggests.

copyright Sergiy Serdyuk/istockphoto.com

A study published in PLOS Medicine used vital registration and population data from across the United States for 1999-2015 to estimate the number of deaths and loss of life expectancy associated with four different models of concentrations of fine particulate matter pollution, and examine how that has changed over time.

While the current national ambient air quality standard for particle pollution is 12 mcg/m³ in almost all counties, the study found that in 1999, 59% of the 1,339 county units had concentrations above this level. At that time, the population-weighted average fine particulate matter pollution concentration for the entire country was 13.6mcg/m³. The highest level was seen in Fresno county in California, which had a fine particulate pollution concentration of 22.1 mcg/m³.

By 2015, national concentrations had declined to 8.0 mcg/m³, and the lowest observed concentration was 2.8 mcg/m³.

The investigators wrote, “Each model was applied to county-level cardiorespiratory death rates separately by sex and age group (5-year age groups from birth to 85 years and 85 years and older) because death rates vary by age group and sex, as might their associations with air pollution. From each model we estimated age-specific proportional increases in death rates (i.e. rate ratios) for each 1 mcg/m³ of PM_2.5 [fine particulate matter].” The analysis revealed that fine particulate matter pollution above the lowest observed concentration of 2.8 mcg/m³ was associated with higher death rates from cardiorespiratory diseases.

Overall, researchers estimated that these higher levels contributed to 15,612 deaths from cardiorespiratory diseases in women and 14,757 deaths in men, representing 2.8% and 2.7% of all cardiorespiratory deaths, respectively. This amounted to 0.15 years of life expectancy lost in women and 0.13 years lost in men.

There was significant variation in the cost to life expectancy around the country. In the midwestern and Rocky Mountain counties in states such as New Mexico, Colorado, and Arizona, which had lower levels of air pollution, life expectancy loss was less than 0.05 years. But in southern states where the air pollution levels were highest, such as Arkansas, Oklahoma, Alabama, and around Los Angeles, the life expectancy loss was greater than 0.3 years.

“While current PM_2.5 pollution is responsible for a significant mortality burden and loss of longevity, reductions in pollution since the late 1990s have benefited virtually the entire country, with the exception of 14 counties where PM_2.5 increased slightly over this period,” wrote James E. Bennett, PhD, of the School of Public Health at Imperial College London and coauthors.

The primary limitation of the study is that this association between air pollution and cardiorespiratory health or life expectancy cannot be shown to be causal. Other pollutants and other environmental and behavioral factors that impact cardiorespiratory health may be significant. For example, including ozone and nitrogen dioxide levels in the models could result in different results in terms of the impact of PM2.5 on cardiorespiratory health.

The data highlighted that life expectancy loss associated with air pollution was larger in lower-income counties, those where a higher proportion of the population had a family income below the poverty line, and those where a higher proportion of the population were black or African American.

“This inequality in mortality burden occurs because lower-income counties, those with more poverty, with a greater proportion who are of black or African American race, or with a lower proportion who have graduated high school tend to have higher baseline death rates at any pollution level because of conditions associated with these covariates and hence experience a larger absolute number of deaths as a result of air pollution,” the authors wrote.

The study was funded by the U.S. Environmental Protection Agency and the Wellcome Trust. One author declared grants and personal fees from private industry, outside the submitted work.
 

SOURCE: Bennett JE et al. PLoS Med. 2019 Jul 23. doi: 10.1371/journal.pmed.1002856.

A landmark study of advanced endometrial cancer, GOG 258, was published in the New England Journal of Medicine this summer.¹ This clinical trial compared the use of carboplatin and paclitaxel chemotherapy with a combination of chemotherapy with external beam radiation, exploring the notion of “more is better.” The results of the trial revealed that the “more” (chemotherapy with external beam radiation) was no better than chemotherapy alone with respect to overall survival. These results have challenged a creeping dogma in gynecologic oncology, which has seen many providers embrace combination therapy, particularly for patients with stage III (node-positive) endometrial cancer, a group of patients who made up approximately three-quarters of GOG 258’s study population. Many have been left searching for justification of their early adoption of combination therapy before the results of a trial such as this were available. For me it also raised a slightly different question: In the light of these results, what IS the role of para-aortic lymphadenectomy in the staging of endometrial cancers? If radiation to the nodal basins is no longer part of adjuvant therapy, then is pelvic lymphadenectomy or pelvic-only sentinel lymph node (SLN) biopsy enough in determining which patients need chemotherapy?

It was in the 1980s that the removal of clinically normal para-aortic lymph nodes (those residing between the renal and proximal common iliac vessels) became a part of surgical staging. This practice was endorsed by the International Federation of Gynecology and Obstetrics (FIGO) and the Gynecologic Oncology Group (GOG) surgical committee in response to findings that 11% of women with clinical stage I endometrial cancer had microscopic lymph node metastases which were discovered only with routine pathologic evaluation of these tissues. Among those with pelvic lymph node metastases (stage IIIC disease), approximately one-third also harbored disease in para-aortic nodal regions.² Among all patients with endometrial cancer, including those with low-grade disease, only a small fraction (approximately 2%) have isolated para-aortic lymph nodes (positive para-aortic nodes, but negative pelvic nodes). However, among patients with deeply invasive higher-grade tumors, the likelihood of discovering isolated para-aortic metastases is higher at approximately 16%.³ Therefore, the dominant pattern of lymph node metastases and lymphatic dissemination of endometrial cancer appears to be via the parametrial channels laterally towards the pelvic basins, and then sequentially to the para-aortic regions. The direct lymphatic pathway to the para-aortic basins from the uterine fundus through the adnexal lymphatics misses the pelvic regions altogether and may seen logical, but actually is observed fairly infrequently.⁴

Over the subsequent decades, there have been debates and schools of thought regarding what is the optimal degree of lymphatic dissection for endometrial cancer staging. Some advocated for full pelvic and infrarenal para-aortic nodal dissections in all patients, including even those in the lowest risk for metastases. Others advocated for a more limited, inframesenteric para-aortic nodal dissection, although the origins of such a distinction appear to be largely arbitrary. The inferior mesenteric artery is not a physiologic landmark for lymphatic pathways, and approximately half of para-aortic metastases are located above the level of the inferior mesenteric artery. This limited sampling may have been preferred because of relative ease of dissection rather than diagnostic or therapeutic efficacy.

As the population became more obese, making para-aortic nodal dissections less feasible, and laparoscopic staging became accepted as the standard of care in endometrial cancer staging, there was a further push towards limiting the scope of lymphadenectomy. Selective algorithms, such as the so-called “Mayo clinic criteria,” were widely adopted. In this approach, gynecologic oncologists perform full pelvic and infrarenal para-aortic lymphadenectomies but only in the presence of a high-risk uterine feature such as tumor size greater than 2 cm, deep myometrial invasion, or grade 3 histology.³ While this reduced the number of para-aortic dissections being performed, it did not eliminate them, as approximately 40% of patients with endometrial cancer meet at least one of those criteria.

At this same time, we learned something else critical about the benefits, or lack thereof, of lymphadenectomy. Two landmark surgical-staging trials were published in 2009 which randomly assigned women to hysterectomy with lymphadenectomy or hysterectomy alone, and found no survival benefit for lymphadenectomy.^5,6 While these trial results initially were met with noisy backlash, particularly from those who had legitimate concerns regarding study design and conclusions that reach beyond the scope of this column, ultimately their findings (that there is no therapeutic benefit to surgically removing clinically normal lymph nodes) has become largely accepted. The subsequent findings of the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial further support this, as there was no difference in survival found between patients who were randomly assigned to laparoscopic versus open staging for endometrial cancer, even despite a significantly lower rate of lymphadenectomy among the laparoscopic arm.⁷

SLN biopsy, in which the specific nodes which drain the uterus are selectively removed, represents the most recent development in lymph node assessment for endometrial cancer. On average, only three lymph nodes are removed per patient, and para-aortic nodes infrequently are removed, because it is rare that lymphatic pathways drain directly into the aortic basins after cervical injection. Yet despite this more limited dissection of lymph nodes, especially para-aortic, with SLN biopsy, surgeons still observe similar rates of IIIC disease, compared with full lymphadenectomy, suggesting that the presence or absence of lymphatic metastases still is able to be adequately determined. SLN biopsy misses only 3% of lymphatic disease.⁸ What is of particular interest to practitioners of the SLN approach is that “atypical” pathways are discovered approximately 20% of the time, and nodes are harvested from locations such as the presacral space or medial to the internal iliac vessels. These nodes are in locations previously overlooked by even the most comprehensive pelvic and para-aortic lymphadenectomy. Therefore, while the para-aortic nodes may not be systematically removed with SLN biopsy, new and arguably more relevant regions are interrogated, which might explain its equivalent diagnostic virtue.

With this evolution in surgical-staging practice, what we have come to recognize is that the role of lymph node assessment is predominantly, if not exclusively, diagnostic. It can help us determine which patients are at risk for distant relapse and therefore candidates for systemic therapy (chemotherapy), versus those whose risk is predominantly of local relapse and can be adequately treated with local therapies alone, such as vaginal radiation. This brings us to the results of GOG 258. If defining the specific and complete extent of lymph node metastases (as if that was ever truly what surgeons were doing) is no longer necessary to guide the prescription and extent of external beam radiation, then lymph node dissection need only inform us of whether or not there are nodal metastases, not specifically the location of those nodal metastases. The prescription of chemotherapy is the same whether the disease is limited to the pelvic nodes or also includes the para-aortic nodes. While GOG 258 discovered more para-aortic failures among the chemotherapy-alone group, suggesting there may be some therapeutic role of radiation in preventing this, it should be noted that these para-aortic relapses did not negatively impact relapse-free survival, and these patients still can presumably be salvaged with external beam radiation to the site of para-aortic relapse.

It would seem logical that the results of GOG 258 further limit the potential role of para-aortic lymphadenectomy in women with clinical stage I disease. Perhaps para-aortic dissection can be limited to women who are at highest risk for isolated para-aortic disease, such as those with deeply invasive high-grade tumors not successfully mapped with the highly targeted sentinel node biopsy technique? Most clinicians look forward to an era in which we no longer rely on crude dissections of disease-free tissue just to prove they are disease free, but instead can utilize more sophisticated diagnostic methods to recognize disseminated disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2019 Jun 13;380(24):2317-26.

2. Cancer. 1987 Oct 15;60(8 Suppl):2035-41.

3. Gynecol Oncol. 2008;109(1):11-8.

4. Int J Gynecol Cancer. 2019 Mar;29(3):613-21.

5. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

6. Lancet. 2009 Jan 10;373(9658):125-36.

7. JAMA. 2017 Mar 28;317(12):1224-33.

8. Lancet Oncol. 2017 Mar;18(3):384-92.

A landmark study of advanced endometrial cancer, GOG 258, was published in the New England Journal of Medicine this summer.¹ This clinical trial compared the use of carboplatin and paclitaxel chemotherapy with a combination of chemotherapy with external beam radiation, exploring the notion of “more is better.” The results of the trial revealed that the “more” (chemotherapy with external beam radiation) was no better than chemotherapy alone with respect to overall survival. These results have challenged a creeping dogma in gynecologic oncology, which has seen many providers embrace combination therapy, particularly for patients with stage III (node-positive) endometrial cancer, a group of patients who made up approximately three-quarters of GOG 258’s study population. Many have been left searching for justification of their early adoption of combination therapy before the results of a trial such as this were available. For me it also raised a slightly different question: In the light of these results, what IS the role of para-aortic lymphadenectomy in the staging of endometrial cancers? If radiation to the nodal basins is no longer part of adjuvant therapy, then is pelvic lymphadenectomy or pelvic-only sentinel lymph node (SLN) biopsy enough in determining which patients need chemotherapy?

It was in the 1980s that the removal of clinically normal para-aortic lymph nodes (those residing between the renal and proximal common iliac vessels) became a part of surgical staging. This practice was endorsed by the International Federation of Gynecology and Obstetrics (FIGO) and the Gynecologic Oncology Group (GOG) surgical committee in response to findings that 11% of women with clinical stage I endometrial cancer had microscopic lymph node metastases which were discovered only with routine pathologic evaluation of these tissues. Among those with pelvic lymph node metastases (stage IIIC disease), approximately one-third also harbored disease in para-aortic nodal regions.² Among all patients with endometrial cancer, including those with low-grade disease, only a small fraction (approximately 2%) have isolated para-aortic lymph nodes (positive para-aortic nodes, but negative pelvic nodes). However, among patients with deeply invasive higher-grade tumors, the likelihood of discovering isolated para-aortic metastases is higher at approximately 16%.³ Therefore, the dominant pattern of lymph node metastases and lymphatic dissemination of endometrial cancer appears to be via the parametrial channels laterally towards the pelvic basins, and then sequentially to the para-aortic regions. The direct lymphatic pathway to the para-aortic basins from the uterine fundus through the adnexal lymphatics misses the pelvic regions altogether and may seen logical, but actually is observed fairly infrequently.⁴

Over the subsequent decades, there have been debates and schools of thought regarding what is the optimal degree of lymphatic dissection for endometrial cancer staging. Some advocated for full pelvic and infrarenal para-aortic nodal dissections in all patients, including even those in the lowest risk for metastases. Others advocated for a more limited, inframesenteric para-aortic nodal dissection, although the origins of such a distinction appear to be largely arbitrary. The inferior mesenteric artery is not a physiologic landmark for lymphatic pathways, and approximately half of para-aortic metastases are located above the level of the inferior mesenteric artery. This limited sampling may have been preferred because of relative ease of dissection rather than diagnostic or therapeutic efficacy.

As the population became more obese, making para-aortic nodal dissections less feasible, and laparoscopic staging became accepted as the standard of care in endometrial cancer staging, there was a further push towards limiting the scope of lymphadenectomy. Selective algorithms, such as the so-called “Mayo clinic criteria,” were widely adopted. In this approach, gynecologic oncologists perform full pelvic and infrarenal para-aortic lymphadenectomies but only in the presence of a high-risk uterine feature such as tumor size greater than 2 cm, deep myometrial invasion, or grade 3 histology.³ While this reduced the number of para-aortic dissections being performed, it did not eliminate them, as approximately 40% of patients with endometrial cancer meet at least one of those criteria.

At this same time, we learned something else critical about the benefits, or lack thereof, of lymphadenectomy. Two landmark surgical-staging trials were published in 2009 which randomly assigned women to hysterectomy with lymphadenectomy or hysterectomy alone, and found no survival benefit for lymphadenectomy.^5,6 While these trial results initially were met with noisy backlash, particularly from those who had legitimate concerns regarding study design and conclusions that reach beyond the scope of this column, ultimately their findings (that there is no therapeutic benefit to surgically removing clinically normal lymph nodes) has become largely accepted. The subsequent findings of the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial further support this, as there was no difference in survival found between patients who were randomly assigned to laparoscopic versus open staging for endometrial cancer, even despite a significantly lower rate of lymphadenectomy among the laparoscopic arm.⁷

SLN biopsy, in which the specific nodes which drain the uterus are selectively removed, represents the most recent development in lymph node assessment for endometrial cancer. On average, only three lymph nodes are removed per patient, and para-aortic nodes infrequently are removed, because it is rare that lymphatic pathways drain directly into the aortic basins after cervical injection. Yet despite this more limited dissection of lymph nodes, especially para-aortic, with SLN biopsy, surgeons still observe similar rates of IIIC disease, compared with full lymphadenectomy, suggesting that the presence or absence of lymphatic metastases still is able to be adequately determined. SLN biopsy misses only 3% of lymphatic disease.⁸ What is of particular interest to practitioners of the SLN approach is that “atypical” pathways are discovered approximately 20% of the time, and nodes are harvested from locations such as the presacral space or medial to the internal iliac vessels. These nodes are in locations previously overlooked by even the most comprehensive pelvic and para-aortic lymphadenectomy. Therefore, while the para-aortic nodes may not be systematically removed with SLN biopsy, new and arguably more relevant regions are interrogated, which might explain its equivalent diagnostic virtue.

With this evolution in surgical-staging practice, what we have come to recognize is that the role of lymph node assessment is predominantly, if not exclusively, diagnostic. It can help us determine which patients are at risk for distant relapse and therefore candidates for systemic therapy (chemotherapy), versus those whose risk is predominantly of local relapse and can be adequately treated with local therapies alone, such as vaginal radiation. This brings us to the results of GOG 258. If defining the specific and complete extent of lymph node metastases (as if that was ever truly what surgeons were doing) is no longer necessary to guide the prescription and extent of external beam radiation, then lymph node dissection need only inform us of whether or not there are nodal metastases, not specifically the location of those nodal metastases. The prescription of chemotherapy is the same whether the disease is limited to the pelvic nodes or also includes the para-aortic nodes. While GOG 258 discovered more para-aortic failures among the chemotherapy-alone group, suggesting there may be some therapeutic role of radiation in preventing this, it should be noted that these para-aortic relapses did not negatively impact relapse-free survival, and these patients still can presumably be salvaged with external beam radiation to the site of para-aortic relapse.

It would seem logical that the results of GOG 258 further limit the potential role of para-aortic lymphadenectomy in women with clinical stage I disease. Perhaps para-aortic dissection can be limited to women who are at highest risk for isolated para-aortic disease, such as those with deeply invasive high-grade tumors not successfully mapped with the highly targeted sentinel node biopsy technique? Most clinicians look forward to an era in which we no longer rely on crude dissections of disease-free tissue just to prove they are disease free, but instead can utilize more sophisticated diagnostic methods to recognize disseminated disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2019 Jun 13;380(24):2317-26.

2. Cancer. 1987 Oct 15;60(8 Suppl):2035-41.

3. Gynecol Oncol. 2008;109(1):11-8.

4. Int J Gynecol Cancer. 2019 Mar;29(3):613-21.

5. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

6. Lancet. 2009 Jan 10;373(9658):125-36.

7. JAMA. 2017 Mar 28;317(12):1224-33.

8. Lancet Oncol. 2017 Mar;18(3):384-92.

A landmark study of advanced endometrial cancer, GOG 258, was published in the New England Journal of Medicine this summer.¹ This clinical trial compared the use of carboplatin and paclitaxel chemotherapy with a combination of chemotherapy with external beam radiation, exploring the notion of “more is better.” The results of the trial revealed that the “more” (chemotherapy with external beam radiation) was no better than chemotherapy alone with respect to overall survival. These results have challenged a creeping dogma in gynecologic oncology, which has seen many providers embrace combination therapy, particularly for patients with stage III (node-positive) endometrial cancer, a group of patients who made up approximately three-quarters of GOG 258’s study population. Many have been left searching for justification of their early adoption of combination therapy before the results of a trial such as this were available. For me it also raised a slightly different question: In the light of these results, what IS the role of para-aortic lymphadenectomy in the staging of endometrial cancers? If radiation to the nodal basins is no longer part of adjuvant therapy, then is pelvic lymphadenectomy or pelvic-only sentinel lymph node (SLN) biopsy enough in determining which patients need chemotherapy?

It was in the 1980s that the removal of clinically normal para-aortic lymph nodes (those residing between the renal and proximal common iliac vessels) became a part of surgical staging. This practice was endorsed by the International Federation of Gynecology and Obstetrics (FIGO) and the Gynecologic Oncology Group (GOG) surgical committee in response to findings that 11% of women with clinical stage I endometrial cancer had microscopic lymph node metastases which were discovered only with routine pathologic evaluation of these tissues. Among those with pelvic lymph node metastases (stage IIIC disease), approximately one-third also harbored disease in para-aortic nodal regions.² Among all patients with endometrial cancer, including those with low-grade disease, only a small fraction (approximately 2%) have isolated para-aortic lymph nodes (positive para-aortic nodes, but negative pelvic nodes). However, among patients with deeply invasive higher-grade tumors, the likelihood of discovering isolated para-aortic metastases is higher at approximately 16%.³ Therefore, the dominant pattern of lymph node metastases and lymphatic dissemination of endometrial cancer appears to be via the parametrial channels laterally towards the pelvic basins, and then sequentially to the para-aortic regions. The direct lymphatic pathway to the para-aortic basins from the uterine fundus through the adnexal lymphatics misses the pelvic regions altogether and may seen logical, but actually is observed fairly infrequently.⁴

Over the subsequent decades, there have been debates and schools of thought regarding what is the optimal degree of lymphatic dissection for endometrial cancer staging. Some advocated for full pelvic and infrarenal para-aortic nodal dissections in all patients, including even those in the lowest risk for metastases. Others advocated for a more limited, inframesenteric para-aortic nodal dissection, although the origins of such a distinction appear to be largely arbitrary. The inferior mesenteric artery is not a physiologic landmark for lymphatic pathways, and approximately half of para-aortic metastases are located above the level of the inferior mesenteric artery. This limited sampling may have been preferred because of relative ease of dissection rather than diagnostic or therapeutic efficacy.

As the population became more obese, making para-aortic nodal dissections less feasible, and laparoscopic staging became accepted as the standard of care in endometrial cancer staging, there was a further push towards limiting the scope of lymphadenectomy. Selective algorithms, such as the so-called “Mayo clinic criteria,” were widely adopted. In this approach, gynecologic oncologists perform full pelvic and infrarenal para-aortic lymphadenectomies but only in the presence of a high-risk uterine feature such as tumor size greater than 2 cm, deep myometrial invasion, or grade 3 histology.³ While this reduced the number of para-aortic dissections being performed, it did not eliminate them, as approximately 40% of patients with endometrial cancer meet at least one of those criteria.

At this same time, we learned something else critical about the benefits, or lack thereof, of lymphadenectomy. Two landmark surgical-staging trials were published in 2009 which randomly assigned women to hysterectomy with lymphadenectomy or hysterectomy alone, and found no survival benefit for lymphadenectomy.^5,6 While these trial results initially were met with noisy backlash, particularly from those who had legitimate concerns regarding study design and conclusions that reach beyond the scope of this column, ultimately their findings (that there is no therapeutic benefit to surgically removing clinically normal lymph nodes) has become largely accepted. The subsequent findings of the Laparoscopic Approach to Cancer of the Endometrium (LACE) trial further support this, as there was no difference in survival found between patients who were randomly assigned to laparoscopic versus open staging for endometrial cancer, even despite a significantly lower rate of lymphadenectomy among the laparoscopic arm.⁷

SLN biopsy, in which the specific nodes which drain the uterus are selectively removed, represents the most recent development in lymph node assessment for endometrial cancer. On average, only three lymph nodes are removed per patient, and para-aortic nodes infrequently are removed, because it is rare that lymphatic pathways drain directly into the aortic basins after cervical injection. Yet despite this more limited dissection of lymph nodes, especially para-aortic, with SLN biopsy, surgeons still observe similar rates of IIIC disease, compared with full lymphadenectomy, suggesting that the presence or absence of lymphatic metastases still is able to be adequately determined. SLN biopsy misses only 3% of lymphatic disease.⁸ What is of particular interest to practitioners of the SLN approach is that “atypical” pathways are discovered approximately 20% of the time, and nodes are harvested from locations such as the presacral space or medial to the internal iliac vessels. These nodes are in locations previously overlooked by even the most comprehensive pelvic and para-aortic lymphadenectomy. Therefore, while the para-aortic nodes may not be systematically removed with SLN biopsy, new and arguably more relevant regions are interrogated, which might explain its equivalent diagnostic virtue.

With this evolution in surgical-staging practice, what we have come to recognize is that the role of lymph node assessment is predominantly, if not exclusively, diagnostic. It can help us determine which patients are at risk for distant relapse and therefore candidates for systemic therapy (chemotherapy), versus those whose risk is predominantly of local relapse and can be adequately treated with local therapies alone, such as vaginal radiation. This brings us to the results of GOG 258. If defining the specific and complete extent of lymph node metastases (as if that was ever truly what surgeons were doing) is no longer necessary to guide the prescription and extent of external beam radiation, then lymph node dissection need only inform us of whether or not there are nodal metastases, not specifically the location of those nodal metastases. The prescription of chemotherapy is the same whether the disease is limited to the pelvic nodes or also includes the para-aortic nodes. While GOG 258 discovered more para-aortic failures among the chemotherapy-alone group, suggesting there may be some therapeutic role of radiation in preventing this, it should be noted that these para-aortic relapses did not negatively impact relapse-free survival, and these patients still can presumably be salvaged with external beam radiation to the site of para-aortic relapse.

It would seem logical that the results of GOG 258 further limit the potential role of para-aortic lymphadenectomy in women with clinical stage I disease. Perhaps para-aortic dissection can be limited to women who are at highest risk for isolated para-aortic disease, such as those with deeply invasive high-grade tumors not successfully mapped with the highly targeted sentinel node biopsy technique? Most clinicians look forward to an era in which we no longer rely on crude dissections of disease-free tissue just to prove they are disease free, but instead can utilize more sophisticated diagnostic methods to recognize disseminated disease.
 

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. Email her at obnews@mdedge.com.

References

1. N Engl J Med. 2019 Jun 13;380(24):2317-26.

2. Cancer. 1987 Oct 15;60(8 Suppl):2035-41.

3. Gynecol Oncol. 2008;109(1):11-8.

4. Int J Gynecol Cancer. 2019 Mar;29(3):613-21.

5. J Natl Cancer Inst. 2008 Dec 3;100(23):1707-16.

6. Lancet. 2009 Jan 10;373(9658):125-36.

7. JAMA. 2017 Mar 28;317(12):1224-33.

8. Lancet Oncol. 2017 Mar;18(3):384-92.

The use of administrative data may improve the accuracy and reduce costs of oncology clinical trial economic analyses, according to a retrospective study.

“We investigated whether administrative data could improve the performance of cancer trial economic analysis,” Timothy P. Hanna, MD, MSc, PhD, of Queen’s University in Kingston, Ont., and colleagues wrote in the Journal of Oncology Practice.

The researchers linked clinical trial and health administrative data to evaluate the utility of administrative data in a group of 572 patients with previously treated metastatic colorectal cancer.

The phase 3 trial assessed cetuximab plus best supportive care versus best supportive care alone in these patients. The trial data set was used to obtain information related to resource utilization, such as hospitalization or treatment costs, in addition to clinical reports, such as vital status.

Several measures were estimated by the team, including the incremental cost-effectiveness ratio (ICER) and total costs.

After analysis, the researchers found that ICER measures were comparable with the use of administrative data versus trial data alone ($164,378 vs. $211,128 per QALY added up to last contact).

“Up to trial date of last contact, vital status was in agreement for more than 96% of patients,” Dr. Hanna and colleagues reported.

These findings highlight the potential utility of administrative data in reducing the costs of collecting applicable data from clinical trials alone.

“A harmonized approach has the potential to provide more complete information on clinical trial participants at reduced cost,” they concluded.

The study was funded by the Institute for Clinical Evaluative Sciences and Queen’s University. The authors reported financial affiliations with Amgen, Janssen, Novartis, and UpToDate.

SOURCE: Hanna TP et al. J Oncol Pract. 2019 Jul 15. doi: 10.1200/JOP.18.00691.

The use of administrative data may improve the accuracy and reduce costs of oncology clinical trial economic analyses, according to a retrospective study.

“We investigated whether administrative data could improve the performance of cancer trial economic analysis,” Timothy P. Hanna, MD, MSc, PhD, of Queen’s University in Kingston, Ont., and colleagues wrote in the Journal of Oncology Practice.

The researchers linked clinical trial and health administrative data to evaluate the utility of administrative data in a group of 572 patients with previously treated metastatic colorectal cancer.

The phase 3 trial assessed cetuximab plus best supportive care versus best supportive care alone in these patients. The trial data set was used to obtain information related to resource utilization, such as hospitalization or treatment costs, in addition to clinical reports, such as vital status.

Several measures were estimated by the team, including the incremental cost-effectiveness ratio (ICER) and total costs.

After analysis, the researchers found that ICER measures were comparable with the use of administrative data versus trial data alone ($164,378 vs. $211,128 per QALY added up to last contact).

“Up to trial date of last contact, vital status was in agreement for more than 96% of patients,” Dr. Hanna and colleagues reported.

These findings highlight the potential utility of administrative data in reducing the costs of collecting applicable data from clinical trials alone.

“A harmonized approach has the potential to provide more complete information on clinical trial participants at reduced cost,” they concluded.

The study was funded by the Institute for Clinical Evaluative Sciences and Queen’s University. The authors reported financial affiliations with Amgen, Janssen, Novartis, and UpToDate.

SOURCE: Hanna TP et al. J Oncol Pract. 2019 Jul 15. doi: 10.1200/JOP.18.00691.

The use of administrative data may improve the accuracy and reduce costs of oncology clinical trial economic analyses, according to a retrospective study.

“We investigated whether administrative data could improve the performance of cancer trial economic analysis,” Timothy P. Hanna, MD, MSc, PhD, of Queen’s University in Kingston, Ont., and colleagues wrote in the Journal of Oncology Practice.

The researchers linked clinical trial and health administrative data to evaluate the utility of administrative data in a group of 572 patients with previously treated metastatic colorectal cancer.

The phase 3 trial assessed cetuximab plus best supportive care versus best supportive care alone in these patients. The trial data set was used to obtain information related to resource utilization, such as hospitalization or treatment costs, in addition to clinical reports, such as vital status.

Several measures were estimated by the team, including the incremental cost-effectiveness ratio (ICER) and total costs.

After analysis, the researchers found that ICER measures were comparable with the use of administrative data versus trial data alone ($164,378 vs. $211,128 per QALY added up to last contact).

“Up to trial date of last contact, vital status was in agreement for more than 96% of patients,” Dr. Hanna and colleagues reported.

These findings highlight the potential utility of administrative data in reducing the costs of collecting applicable data from clinical trials alone.

“A harmonized approach has the potential to provide more complete information on clinical trial participants at reduced cost,” they concluded.

The study was funded by the Institute for Clinical Evaluative Sciences and Queen’s University. The authors reported financial affiliations with Amgen, Janssen, Novartis, and UpToDate.

SOURCE: Hanna TP et al. J Oncol Pract. 2019 Jul 15. doi: 10.1200/JOP.18.00691.

The Food and Drug Administration has expanded the indication for apremilast (Otezla) to include the treatment of oral ulcers associated with Behçet’s disease in adults, according to an announcement from the manufacturer, Celgene.

FDA approval was based on results of the randomized, placebo-controlled, double-blind, phase 3 RELIEF trial, in which 207 patients with Behçet’s disease with active ulcers underwent treatment for 12 weeks with 30 mg apremilast or placebo. When measured on a visual analog scale, the reduction in pain from oral ulcers after 12 weeks in patients receiving apremilast was 42.7 points, compared with 18.7 points in the placebo group. Just over 50% of apremilast patients achieved complete response by week 12, compared with 22.3% in the placebo group.

The most common adverse events associated with apremilast during RELIEF were diarrhea, nausea, headache, and upper respiratory infection. This was consistent with apremilast’s known safety profile.


Apremilast is also indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for patients with active psoriatic arthritis.

“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s disease and have an important negative impact on the quality of life for these patients. In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available,” Yusuf Yazici, MD, clinical associate professor in the department of medicine at New York University, said in the announcement.

lfranki@mdedge.com

The Food and Drug Administration has expanded the indication for apremilast (Otezla) to include the treatment of oral ulcers associated with Behçet’s disease in adults, according to an announcement from the manufacturer, Celgene.

FDA approval was based on results of the randomized, placebo-controlled, double-blind, phase 3 RELIEF trial, in which 207 patients with Behçet’s disease with active ulcers underwent treatment for 12 weeks with 30 mg apremilast or placebo. When measured on a visual analog scale, the reduction in pain from oral ulcers after 12 weeks in patients receiving apremilast was 42.7 points, compared with 18.7 points in the placebo group. Just over 50% of apremilast patients achieved complete response by week 12, compared with 22.3% in the placebo group.

The most common adverse events associated with apremilast during RELIEF were diarrhea, nausea, headache, and upper respiratory infection. This was consistent with apremilast’s known safety profile.


Apremilast is also indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for patients with active psoriatic arthritis.

“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s disease and have an important negative impact on the quality of life for these patients. In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available,” Yusuf Yazici, MD, clinical associate professor in the department of medicine at New York University, said in the announcement.

lfranki@mdedge.com

The Food and Drug Administration has expanded the indication for apremilast (Otezla) to include the treatment of oral ulcers associated with Behçet’s disease in adults, according to an announcement from the manufacturer, Celgene.

FDA approval was based on results of the randomized, placebo-controlled, double-blind, phase 3 RELIEF trial, in which 207 patients with Behçet’s disease with active ulcers underwent treatment for 12 weeks with 30 mg apremilast or placebo. When measured on a visual analog scale, the reduction in pain from oral ulcers after 12 weeks in patients receiving apremilast was 42.7 points, compared with 18.7 points in the placebo group. Just over 50% of apremilast patients achieved complete response by week 12, compared with 22.3% in the placebo group.

The most common adverse events associated with apremilast during RELIEF were diarrhea, nausea, headache, and upper respiratory infection. This was consistent with apremilast’s known safety profile.


Apremilast is also indicated for treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, and for patients with active psoriatic arthritis.

“Oral ulcers are a recurring and debilitating manifestation that affects nearly everyone living with Behçet’s disease and have an important negative impact on the quality of life for these patients. In the clinical trial, Otezla demonstrated improvements in measures of oral ulcers at week 12. Otezla has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available,” Yusuf Yazici, MD, clinical associate professor in the department of medicine at New York University, said in the announcement.

lfranki@mdedge.com

Having a first-degree relative with amyotrophic lateral sclerosis (ALS) increases the lifetime risk of developing the condition, even in the absence of a known ALS-associated genetic mutation, according to a recent Irish population–based study.

designer491/Thinkstock

Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).

Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.

For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.

In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.

Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.

The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”


Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.

“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”

Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.

koakes@mdedge.com

SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.

Having a first-degree relative with amyotrophic lateral sclerosis (ALS) increases the lifetime risk of developing the condition, even in the absence of a known ALS-associated genetic mutation, according to a recent Irish population–based study.

designer491/Thinkstock

Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).

Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.

For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.

In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.

Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.

The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”


Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.

“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”

Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.

koakes@mdedge.com

SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.

Having a first-degree relative with amyotrophic lateral sclerosis (ALS) increases the lifetime risk of developing the condition, even in the absence of a known ALS-associated genetic mutation, according to a recent Irish population–based study.

designer491/Thinkstock

Among first-degree relatives of individuals with ALS whose genetic status was unknown, the lifetime risk of developing ALS was 1.4%, compared with 0.3% in the general population (P less than .001).

Overall, lifetime heritability for the 1,117 patients in the heritability study cohort was 52.3% (95% confidence interval, 42.9%-61.7%). The highest heritability was seen in mother-daughter dyads; here, the concordance rate for ALS was 2.6% and the heritability estimate was 66.2% (95% CI, 58.5%-73.9%), “pointing to a previously unrecognized sex-mediated association with disease heritability,” Marie Ryan, MD, and coauthors at Trinity College Dublin wrote in JAMA Neurology.

For the purposes of this study, heritability was defined as “the proportion of variance in liability that is attributable to additive genetic factors,” explained the investigators. Their model was applied to 1,123 Irish patients with incident ALS over a 10-year study period, drawing on a national database. Complete medical histories were available for both parents of every individual in the cohort, and the investigators identified 32 parent-offspring dyads with ALS.

In their assessment of “liability” for ALS, Dr. Ryan and colleagues accounted for age-specific and sex-specific ALS incidence rates, using a well-delineated United States reference population. They also took into account competing mortality risks that might intervene before an individual developed ALS.

Although mother-daughter dyads yielded the highest heritability estimates, heritability was also elevated among father-son dyads, at 50.1% (95% CI, 42.0%-59.4%). Opposite-sex dyads (mother-son and father-daughter) yielded similar, and lower, heritability estimates of 34%-38%. Dr. Ryan and coinvestigators acknowledged that female sex hormones might play a role in mediating risk for ALS, but the contribution and mechanism are currently unknown.

The investigators identified 674 patients in the cohort who had been tested for C9orf72; large repeat expansions in the GGGGCC segment of this gene are known to cause ALS. In all, 69 patients were C9orf72 positive, and 14 of these individuals (20.3%) reported that one parent had ALS. Among the entire cohort, 23 of the 32 patients with parents who also had ALS had C9orf72 testing, and 14 of 23 (60.9%) were positive. This discrepancy, wrote Dr. Ryan and coauthors, suggests that “genetic anticipation or pleiotropic effects may have masked the clinical phenotype in their parents.”


Parents were a mean 69.6 years old at the time of diagnosis, and offspring were a mean 52.0 years old; 56% of patients in the study cohort were male.

“[I]n our study, ALS heritability was assessed for the first time in a population in whom genetic mutations have been excluded,” wrote Dr. Ryan and coinvestigators. “We have found that, in the absence of known ALS-associated genetic mutations in the proband, first-degree relatives of individuals with ALS remain at increased risk of developing ALS compared with the general population.”

Dr. Ryan and one coauthor reported receiving funding from Science Foundation Ireland, and one coauthor reported receiving book royalties from Taylor & Francis, and fees from Cytokinetics and Wave Pharmaceuticals. The study was funded by Science Foundation Ireland and the Motor Neurone Disease Association.

koakes@mdedge.com

SOURCE: Ryan M et al. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2044.

To the Editor:

Lupus erythematosus tumidus (LET) is a rarely diagnosed condition that was first described in 1909 by Hoffmann.¹ Limited cases have been reported in the literature, with few documenting the disease in children.² We report a unique clinical case of LET in a 14-year-old adolescent boy that was distributed solely on the hands. With slight heterogeneity in regards to clinical presentation and histopathology, there is a need for further exploration with regard to LET.

A 14-year-old adolescent boy presented to the dermatology clinic with progressive bilateral edema of 1 year’s duration with plaques and some scaling on the dorsal aspects of the digits and the nail bases predominantly on the right hand (Figure 1) and to a lesser extent on the left hand. The edema, erythema, and tenderness started in the right fifth digit; soon after the edema appeared, plaques began to form at the base of each nail bed, and the edema and erythema progressively spread to the other digits. He denied worsening of symptoms when exposed to cold temperatures. A complete review of systems was negative. The differential diagnoses included chilblain lupus erythematosus, perniosis, dermatomyositis, and polymorphous light eruption. A punch biopsy from the right fourth digit was performed.

The lesions of LET have been consistently described in the literature as photosensitive, erythematous, non-scarring, annular plaques and papules commonly occurring on the head/neck and other sun-exposed areas that do not cause hypopigmentation.³ Treatment of LET consists of systemic treatment with antimalarial drugs, sunscreens, and topical steroids for flares.

Lupus erythematosus tumidus is rare in children, with few case reports noted in the literature. Sonntag et al² documented the disease in 3 children ranging from 3 to 8 years of age. Furthermore, Ruiz and Sanchez⁷ reported a case of LET in a 16-year-old adolescent girl. Our case is unique in that the lesions only occurred on the hands, whereas most case reports document distribution of the lesions on the head, neck, face, arms, back, and chest. Our patient’s age and the location of the lesions make it a unique clinical presentation of LET.

Reports in the literature show evidence of heterogeneity in the presentation, classification, and some of the histopathologic features of LET; however, there are minimal data on childhood LET. Further research and investigations are needed to more precisely define this condition.

Acknowledgment

The authors acknowledge Richard Schwartz, MD (Akron, Ohio), for reading the biopsy reports and assisting with photomicrographs.

To the Editor:

Lupus erythematosus tumidus (LET) is a rarely diagnosed condition that was first described in 1909 by Hoffmann.¹ Limited cases have been reported in the literature, with few documenting the disease in children.² We report a unique clinical case of LET in a 14-year-old adolescent boy that was distributed solely on the hands. With slight heterogeneity in regards to clinical presentation and histopathology, there is a need for further exploration with regard to LET.

A 14-year-old adolescent boy presented to the dermatology clinic with progressive bilateral edema of 1 year’s duration with plaques and some scaling on the dorsal aspects of the digits and the nail bases predominantly on the right hand (Figure 1) and to a lesser extent on the left hand. The edema, erythema, and tenderness started in the right fifth digit; soon after the edema appeared, plaques began to form at the base of each nail bed, and the edema and erythema progressively spread to the other digits. He denied worsening of symptoms when exposed to cold temperatures. A complete review of systems was negative. The differential diagnoses included chilblain lupus erythematosus, perniosis, dermatomyositis, and polymorphous light eruption. A punch biopsy from the right fourth digit was performed.

The lesions of LET have been consistently described in the literature as photosensitive, erythematous, non-scarring, annular plaques and papules commonly occurring on the head/neck and other sun-exposed areas that do not cause hypopigmentation.³ Treatment of LET consists of systemic treatment with antimalarial drugs, sunscreens, and topical steroids for flares.

Lupus erythematosus tumidus is rare in children, with few case reports noted in the literature. Sonntag et al² documented the disease in 3 children ranging from 3 to 8 years of age. Furthermore, Ruiz and Sanchez⁷ reported a case of LET in a 16-year-old adolescent girl. Our case is unique in that the lesions only occurred on the hands, whereas most case reports document distribution of the lesions on the head, neck, face, arms, back, and chest. Our patient’s age and the location of the lesions make it a unique clinical presentation of LET.

Reports in the literature show evidence of heterogeneity in the presentation, classification, and some of the histopathologic features of LET; however, there are minimal data on childhood LET. Further research and investigations are needed to more precisely define this condition.

Acknowledgment

The authors acknowledge Richard Schwartz, MD (Akron, Ohio), for reading the biopsy reports and assisting with photomicrographs.

To the Editor:

Lupus erythematosus tumidus (LET) is a rarely diagnosed condition that was first described in 1909 by Hoffmann.¹ Limited cases have been reported in the literature, with few documenting the disease in children.² We report a unique clinical case of LET in a 14-year-old adolescent boy that was distributed solely on the hands. With slight heterogeneity in regards to clinical presentation and histopathology, there is a need for further exploration with regard to LET.

A 14-year-old adolescent boy presented to the dermatology clinic with progressive bilateral edema of 1 year’s duration with plaques and some scaling on the dorsal aspects of the digits and the nail bases predominantly on the right hand (Figure 1) and to a lesser extent on the left hand. The edema, erythema, and tenderness started in the right fifth digit; soon after the edema appeared, plaques began to form at the base of each nail bed, and the edema and erythema progressively spread to the other digits. He denied worsening of symptoms when exposed to cold temperatures. A complete review of systems was negative. The differential diagnoses included chilblain lupus erythematosus, perniosis, dermatomyositis, and polymorphous light eruption. A punch biopsy from the right fourth digit was performed.

The lesions of LET have been consistently described in the literature as photosensitive, erythematous, non-scarring, annular plaques and papules commonly occurring on the head/neck and other sun-exposed areas that do not cause hypopigmentation.³ Treatment of LET consists of systemic treatment with antimalarial drugs, sunscreens, and topical steroids for flares.

Lupus erythematosus tumidus is rare in children, with few case reports noted in the literature. Sonntag et al² documented the disease in 3 children ranging from 3 to 8 years of age. Furthermore, Ruiz and Sanchez⁷ reported a case of LET in a 16-year-old adolescent girl. Our case is unique in that the lesions only occurred on the hands, whereas most case reports document distribution of the lesions on the head, neck, face, arms, back, and chest. Our patient’s age and the location of the lesions make it a unique clinical presentation of LET.

Reports in the literature show evidence of heterogeneity in the presentation, classification, and some of the histopathologic features of LET; however, there are minimal data on childhood LET. Further research and investigations are needed to more precisely define this condition.

Acknowledgment

The authors acknowledge Richard Schwartz, MD (Akron, Ohio), for reading the biopsy reports and assisting with photomicrographs.

If you take a nighttime stroll through the downtown district in any major U.S. city – and certainly in my hometown of Baltimore – you’ll find people sleeping on the streets. Advocates talk about “the homeless mentally ill,” and it’s estimated that a quarter of homeless persons suffer from psychiatric conditions. As psychiatrists, it’s good that we care about the homeless mentally ill. As human beings, shouldn’t we also care about the addicted and indigent homeless? In a country of wealth, it continues to be a disgrace that we have people who live in tent encampments, or who literally sleep on the ground in public places with all their belongings gathered around them.

With 25 contenders for the Democratic presidential nomination, Andrew Yang has caught my attention with his platform for a universal basic income (UBI), or “freedom dividend,” for all adults. Mr. Yang’s premise is a simple one: He’d like to give every person over the age of 18 a $1,000-a-month government-supplied income, funded by a new Value Added Tax (VAT), with no stipulations. I find the concept intriguing. It is the one suggestion that might make a drastic dent in extreme poverty in our country. In theory, every adult would have enough money to afford a place to sleep.

Paul Nestadt, MD, a psychiatrist at Johns Hopkins in Baltimore, agrees with the concept of a universal basic income. “The UBI seems like a humane and egalitarian way to eliminate starvation; it provides a ‘floor’ for poverty. It is a reasonable bare minimum, especially for our patients with serious mental illness who struggle to navigate the bureaucratic steeplechase required to have their basic needs met.” Dr. Nestadt believes that some of the other presidential candidates are supporting policies that would also accomplish this goal.

Marc Nozell/2.0 Generic (CC BY 2.0)

In the “Making Sense” podcast hosted by Sam Harris, “A conversation with Andrew Yang,” Mr. Yang made the point that a UBI is not a new concept – economists and politicians, including Richard Nixon, have supported the idea since the 1960s. A bill proposing a basic income passed in the House of Representatives in 1971 but did not pass in the Senate. In the podcast, Mr. Yang addresses the question of whether people are responsible for their own success, and whether, as Mr. Harris puts it, “it’s just simply wrong to hand out money to people.”

“It’s not as if the truck drivers are about to get dumber and lazier overnight,” Mr. Yang responded. “It’s just that their trucks are going to start driving themselves ... it has nothing to do with their character and work ethic.” He goes on to discuss how workers who lose jobs often leave the workforce and many go on disability.

“Right now, the country’s locked in a struggle between functioning and dysfunction, between reason and unreason, and scarcity and abundance, and scarcity is winning and that’s what we have to reverse through universal basic income; it’s our best way forward.”

If we are optimistic that our government could afford to provide everyone with both a UBI and a universal health plan, such as Medicare-for-all, I still wonder if there might be a societal downside. For self-motivated individuals, a sustenance allowance is unlikely to weaken a drive to achieve. But might there be people who decide they can live on this income, who choose instead to pursue leisure activities rather than pursue education and vocation? Mr. Harris asked Mr. Yang if we would be “subsidizing all the people in their mothers’ basement playing video games.”

Mr. Yang responded, “If you’re getting a thousand dollars a month, then you’re much more likely to get out of your parents’ basement and visit friends and find things to do that are somewhat more social and external-facing. A lot of the reason a lot of these men are retreating is because there’s no real economic security or path forward for them, and they feel much better served by going online and hanging out with their friends and making measurable progress in their gaming environment.”

I like to think that an automatic income would not crush a society’s motivation and productivity, and that money provided to people would fuel education, our economy, an ability to save, and entrepreneurial endeavors, but the truth is that we just don’t know. I would love to see such an experiment done as a large-scale pilot, with the ability to undo the experiment if it fails.

Andrew Yang remains a long shot as the Democratic presidential nominee. His platform, however, is enticing, and he takes on the imminent automation crisis in a way that no one else is actively addressing. His concepts include a degree of humanity that feels welcome when our current president is tweeting that those who are unhappy here should leave. While Mr. Yang is a bit lost in the fray, I do hope his innovative spirit gains some traction.
 

Dr. Miller is the coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016) and has a private practice in Baltimore.

If you take a nighttime stroll through the downtown district in any major U.S. city – and certainly in my hometown of Baltimore – you’ll find people sleeping on the streets. Advocates talk about “the homeless mentally ill,” and it’s estimated that a quarter of homeless persons suffer from psychiatric conditions. As psychiatrists, it’s good that we care about the homeless mentally ill. As human beings, shouldn’t we also care about the addicted and indigent homeless? In a country of wealth, it continues to be a disgrace that we have people who live in tent encampments, or who literally sleep on the ground in public places with all their belongings gathered around them.

With 25 contenders for the Democratic presidential nomination, Andrew Yang has caught my attention with his platform for a universal basic income (UBI), or “freedom dividend,” for all adults. Mr. Yang’s premise is a simple one: He’d like to give every person over the age of 18 a $1,000-a-month government-supplied income, funded by a new Value Added Tax (VAT), with no stipulations. I find the concept intriguing. It is the one suggestion that might make a drastic dent in extreme poverty in our country. In theory, every adult would have enough money to afford a place to sleep.

Paul Nestadt, MD, a psychiatrist at Johns Hopkins in Baltimore, agrees with the concept of a universal basic income. “The UBI seems like a humane and egalitarian way to eliminate starvation; it provides a ‘floor’ for poverty. It is a reasonable bare minimum, especially for our patients with serious mental illness who struggle to navigate the bureaucratic steeplechase required to have their basic needs met.” Dr. Nestadt believes that some of the other presidential candidates are supporting policies that would also accomplish this goal.

Marc Nozell/2.0 Generic (CC BY 2.0)

In the “Making Sense” podcast hosted by Sam Harris, “A conversation with Andrew Yang,” Mr. Yang made the point that a UBI is not a new concept – economists and politicians, including Richard Nixon, have supported the idea since the 1960s. A bill proposing a basic income passed in the House of Representatives in 1971 but did not pass in the Senate. In the podcast, Mr. Yang addresses the question of whether people are responsible for their own success, and whether, as Mr. Harris puts it, “it’s just simply wrong to hand out money to people.”

“It’s not as if the truck drivers are about to get dumber and lazier overnight,” Mr. Yang responded. “It’s just that their trucks are going to start driving themselves ... it has nothing to do with their character and work ethic.” He goes on to discuss how workers who lose jobs often leave the workforce and many go on disability.

“Right now, the country’s locked in a struggle between functioning and dysfunction, between reason and unreason, and scarcity and abundance, and scarcity is winning and that’s what we have to reverse through universal basic income; it’s our best way forward.”

If we are optimistic that our government could afford to provide everyone with both a UBI and a universal health plan, such as Medicare-for-all, I still wonder if there might be a societal downside. For self-motivated individuals, a sustenance allowance is unlikely to weaken a drive to achieve. But might there be people who decide they can live on this income, who choose instead to pursue leisure activities rather than pursue education and vocation? Mr. Harris asked Mr. Yang if we would be “subsidizing all the people in their mothers’ basement playing video games.”

Mr. Yang responded, “If you’re getting a thousand dollars a month, then you’re much more likely to get out of your parents’ basement and visit friends and find things to do that are somewhat more social and external-facing. A lot of the reason a lot of these men are retreating is because there’s no real economic security or path forward for them, and they feel much better served by going online and hanging out with their friends and making measurable progress in their gaming environment.”

I like to think that an automatic income would not crush a society’s motivation and productivity, and that money provided to people would fuel education, our economy, an ability to save, and entrepreneurial endeavors, but the truth is that we just don’t know. I would love to see such an experiment done as a large-scale pilot, with the ability to undo the experiment if it fails.

Andrew Yang remains a long shot as the Democratic presidential nominee. His platform, however, is enticing, and he takes on the imminent automation crisis in a way that no one else is actively addressing. His concepts include a degree of humanity that feels welcome when our current president is tweeting that those who are unhappy here should leave. While Mr. Yang is a bit lost in the fray, I do hope his innovative spirit gains some traction.
 

Dr. Miller is the coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016) and has a private practice in Baltimore.

If you take a nighttime stroll through the downtown district in any major U.S. city – and certainly in my hometown of Baltimore – you’ll find people sleeping on the streets. Advocates talk about “the homeless mentally ill,” and it’s estimated that a quarter of homeless persons suffer from psychiatric conditions. As psychiatrists, it’s good that we care about the homeless mentally ill. As human beings, shouldn’t we also care about the addicted and indigent homeless? In a country of wealth, it continues to be a disgrace that we have people who live in tent encampments, or who literally sleep on the ground in public places with all their belongings gathered around them.

With 25 contenders for the Democratic presidential nomination, Andrew Yang has caught my attention with his platform for a universal basic income (UBI), or “freedom dividend,” for all adults. Mr. Yang’s premise is a simple one: He’d like to give every person over the age of 18 a $1,000-a-month government-supplied income, funded by a new Value Added Tax (VAT), with no stipulations. I find the concept intriguing. It is the one suggestion that might make a drastic dent in extreme poverty in our country. In theory, every adult would have enough money to afford a place to sleep.

Paul Nestadt, MD, a psychiatrist at Johns Hopkins in Baltimore, agrees with the concept of a universal basic income. “The UBI seems like a humane and egalitarian way to eliminate starvation; it provides a ‘floor’ for poverty. It is a reasonable bare minimum, especially for our patients with serious mental illness who struggle to navigate the bureaucratic steeplechase required to have their basic needs met.” Dr. Nestadt believes that some of the other presidential candidates are supporting policies that would also accomplish this goal.

Marc Nozell/2.0 Generic (CC BY 2.0)

In the “Making Sense” podcast hosted by Sam Harris, “A conversation with Andrew Yang,” Mr. Yang made the point that a UBI is not a new concept – economists and politicians, including Richard Nixon, have supported the idea since the 1960s. A bill proposing a basic income passed in the House of Representatives in 1971 but did not pass in the Senate. In the podcast, Mr. Yang addresses the question of whether people are responsible for their own success, and whether, as Mr. Harris puts it, “it’s just simply wrong to hand out money to people.”

“It’s not as if the truck drivers are about to get dumber and lazier overnight,” Mr. Yang responded. “It’s just that their trucks are going to start driving themselves ... it has nothing to do with their character and work ethic.” He goes on to discuss how workers who lose jobs often leave the workforce and many go on disability.

“Right now, the country’s locked in a struggle between functioning and dysfunction, between reason and unreason, and scarcity and abundance, and scarcity is winning and that’s what we have to reverse through universal basic income; it’s our best way forward.”

If we are optimistic that our government could afford to provide everyone with both a UBI and a universal health plan, such as Medicare-for-all, I still wonder if there might be a societal downside. For self-motivated individuals, a sustenance allowance is unlikely to weaken a drive to achieve. But might there be people who decide they can live on this income, who choose instead to pursue leisure activities rather than pursue education and vocation? Mr. Harris asked Mr. Yang if we would be “subsidizing all the people in their mothers’ basement playing video games.”

Mr. Yang responded, “If you’re getting a thousand dollars a month, then you’re much more likely to get out of your parents’ basement and visit friends and find things to do that are somewhat more social and external-facing. A lot of the reason a lot of these men are retreating is because there’s no real economic security or path forward for them, and they feel much better served by going online and hanging out with their friends and making measurable progress in their gaming environment.”

I like to think that an automatic income would not crush a society’s motivation and productivity, and that money provided to people would fuel education, our economy, an ability to save, and entrepreneurial endeavors, but the truth is that we just don’t know. I would love to see such an experiment done as a large-scale pilot, with the ability to undo the experiment if it fails.

Andrew Yang remains a long shot as the Democratic presidential nominee. His platform, however, is enticing, and he takes on the imminent automation crisis in a way that no one else is actively addressing. His concepts include a degree of humanity that feels welcome when our current president is tweeting that those who are unhappy here should leave. While Mr. Yang is a bit lost in the fray, I do hope his innovative spirit gains some traction.
 

Dr. Miller is the coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016) and has a private practice in Baltimore.

Natural disasters such as hurricanes cause delays in radiotherapy delivery for non–small cell lung cancer (NSCLC) that ultimately translate to poorer outcomes, suggests a retrospective cohort study.

“Radiotherapy is particularly vulnerable because it requires dependable electrical power and daily treatment,” lead investigator Leticia M. Nogueira, PhD, Surveillance and Health Services Research Program, American Cancer Society, and colleagues noted. “Disruptions are especially concerning for patients undergoing treatment for locally advanced ... NSCLC because treatment delays as little as 2 days negatively affect survival.”

The investigators used the National Cancer Database to identify patients receiving definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2014 who had at least 1 year of follow-up for vital status.

Each patient undergoing radiotherapy when a hurricane disaster was declared for their facility’s area was matched through propensity scoring with a patient treated during a declaration-free period having similar start month, sex, age, stage, nodal status, and income. Analyses compared 1,734 exposed patients with 1,734 unexposed patients.

Study results reported in JAMA showed that 101 hurricane disaster declarations were made during the study period, and they lasted from 1 day to 69 days. The radiation treatment duration was about 21 days (45%) longer for patients exposed to these declarations than for unexposed counterparts (66.9 vs. 46.2 days; P less than .001).

Over a median follow-up of 15 months, exposed patients were more likely to die (adjusted hazard ratio, 1.19; P = .001). Moreover, risk generally rose with the duration of the declaration, peaking for patients exposed to those lasting 27 days (adjusted relative risk, 1.27).

“Because data on other potentially explanatory factors are lacking, the relative contribution of treatment delay to the observed association cannot be quantified. However, treatment delay is one of the few hurricane-related disruptions that can be prevented,” Dr. Nogueira and colleagues maintain.

“Because no recommended correction for radiotherapy delays exists ... strategies for identifying patients, arranging for transferring treatment, and eliminating patient out-of-network insurance charges should be considered in disaster mitigation planning,” they recommend.

Dr. Nogueira disclosed no relevant conflicts of interest. The investigators conducted the study as part of the in-tramural research program at the American Cancer Society or contributed their time.

SOURCE: Nogueira LM et al. JAMA. 2019 Jul 16;322(3):269-71.

Natural disasters such as hurricanes cause delays in radiotherapy delivery for non–small cell lung cancer (NSCLC) that ultimately translate to poorer outcomes, suggests a retrospective cohort study.

“Radiotherapy is particularly vulnerable because it requires dependable electrical power and daily treatment,” lead investigator Leticia M. Nogueira, PhD, Surveillance and Health Services Research Program, American Cancer Society, and colleagues noted. “Disruptions are especially concerning for patients undergoing treatment for locally advanced ... NSCLC because treatment delays as little as 2 days negatively affect survival.”

The investigators used the National Cancer Database to identify patients receiving definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2014 who had at least 1 year of follow-up for vital status.

Each patient undergoing radiotherapy when a hurricane disaster was declared for their facility’s area was matched through propensity scoring with a patient treated during a declaration-free period having similar start month, sex, age, stage, nodal status, and income. Analyses compared 1,734 exposed patients with 1,734 unexposed patients.

Study results reported in JAMA showed that 101 hurricane disaster declarations were made during the study period, and they lasted from 1 day to 69 days. The radiation treatment duration was about 21 days (45%) longer for patients exposed to these declarations than for unexposed counterparts (66.9 vs. 46.2 days; P less than .001).

Over a median follow-up of 15 months, exposed patients were more likely to die (adjusted hazard ratio, 1.19; P = .001). Moreover, risk generally rose with the duration of the declaration, peaking for patients exposed to those lasting 27 days (adjusted relative risk, 1.27).

“Because data on other potentially explanatory factors are lacking, the relative contribution of treatment delay to the observed association cannot be quantified. However, treatment delay is one of the few hurricane-related disruptions that can be prevented,” Dr. Nogueira and colleagues maintain.

“Because no recommended correction for radiotherapy delays exists ... strategies for identifying patients, arranging for transferring treatment, and eliminating patient out-of-network insurance charges should be considered in disaster mitigation planning,” they recommend.

Dr. Nogueira disclosed no relevant conflicts of interest. The investigators conducted the study as part of the in-tramural research program at the American Cancer Society or contributed their time.

SOURCE: Nogueira LM et al. JAMA. 2019 Jul 16;322(3):269-71.

Natural disasters such as hurricanes cause delays in radiotherapy delivery for non–small cell lung cancer (NSCLC) that ultimately translate to poorer outcomes, suggests a retrospective cohort study.

“Radiotherapy is particularly vulnerable because it requires dependable electrical power and daily treatment,” lead investigator Leticia M. Nogueira, PhD, Surveillance and Health Services Research Program, American Cancer Society, and colleagues noted. “Disruptions are especially concerning for patients undergoing treatment for locally advanced ... NSCLC because treatment delays as little as 2 days negatively affect survival.”

The investigators used the National Cancer Database to identify patients receiving definitive radiotherapy for nonoperative locally advanced NSCLC between 2004 and 2014 who had at least 1 year of follow-up for vital status.

Each patient undergoing radiotherapy when a hurricane disaster was declared for their facility’s area was matched through propensity scoring with a patient treated during a declaration-free period having similar start month, sex, age, stage, nodal status, and income. Analyses compared 1,734 exposed patients with 1,734 unexposed patients.

Study results reported in JAMA showed that 101 hurricane disaster declarations were made during the study period, and they lasted from 1 day to 69 days. The radiation treatment duration was about 21 days (45%) longer for patients exposed to these declarations than for unexposed counterparts (66.9 vs. 46.2 days; P less than .001).

Over a median follow-up of 15 months, exposed patients were more likely to die (adjusted hazard ratio, 1.19; P = .001). Moreover, risk generally rose with the duration of the declaration, peaking for patients exposed to those lasting 27 days (adjusted relative risk, 1.27).

“Because data on other potentially explanatory factors are lacking, the relative contribution of treatment delay to the observed association cannot be quantified. However, treatment delay is one of the few hurricane-related disruptions that can be prevented,” Dr. Nogueira and colleagues maintain.

“Because no recommended correction for radiotherapy delays exists ... strategies for identifying patients, arranging for transferring treatment, and eliminating patient out-of-network insurance charges should be considered in disaster mitigation planning,” they recommend.

Dr. Nogueira disclosed no relevant conflicts of interest. The investigators conducted the study as part of the in-tramural research program at the American Cancer Society or contributed their time.

SOURCE: Nogueira LM et al. JAMA. 2019 Jul 16;322(3):269-71.

The U.S. Preventive Services Task Force has updated and reaffirmed its 2009 recommendation for screening for hepatitis B virus (HBV) infection in pregnant women, according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and other members of the task force.

CDC/Dr. Erskine Palmer

The recommendation statement, published in JAMA, was based on an evidence report and systematic review also published in JAMA. In that review, two studies of fair quality were identified; one included 155,081 infants born to HBV-positive women identified for case management through the national Perinatal Hepatitis B Prevention Program from 1994 to 2008, and the other included 4,446 infants born in a large, regional health care organization in the United States between 1997 and 2010. In both, low rates of perinatal transmission were reported for those periods – between 0.5% and 1.9% – with the rate falling over time.

In the 2009 recommendation, the USPSTF found adequate evidence that serologic testing for hepatitis B surface antigen accurately identifies HBV infection, and that interventions were effective in preventing perinatal transmission. That recommendation has been reaffirmed in the current update, with HBV screening receiving a grade of A, which is the strongest the USPSTF offers.

In a related editorial, Neil S. Silverman, MD, of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles noted several improvements in maternal HBV therapy since the publication of the original 2009 recommendation, including maternal HBV-targeted antiviral therapy during pregnancy as an adjunct to neonatal immunoprophylaxis and the ability to refer women for chronic treatment of their HBV disease to prevent long-term infection complications. The task forces also noted that HBV screening of all pregnant women is mandated by law in 26 states.

One member of the task force reported receiving grants and/or personal fees from Healthwise, another member reported receiving personal fees from UpToDate; a third reported participating in the American Association for the Study of Liver Diseases’ Hepatitis B Guidance and Hepatitis B Systematic Review Group. The evidence and review study was funded by the Agency for Healthcare Research and Quality. Dr. Silverman reported no disclosures.

lfranki@mdedge.com

SOURCes: Owens DK et al. JAMA. 2019 Jul 23. doi: 10.1001/jama.2019.9365; Henderson JT et al. JAMA. 2019 Jul 23;32(4):360-2; Silverman NS. JAMA. 2019 Jul 23;32(4):312-14.

The U.S. Preventive Services Task Force has updated and reaffirmed its 2009 recommendation for screening for hepatitis B virus (HBV) infection in pregnant women, according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and other members of the task force.

CDC/Dr. Erskine Palmer

The recommendation statement, published in JAMA, was based on an evidence report and systematic review also published in JAMA. In that review, two studies of fair quality were identified; one included 155,081 infants born to HBV-positive women identified for case management through the national Perinatal Hepatitis B Prevention Program from 1994 to 2008, and the other included 4,446 infants born in a large, regional health care organization in the United States between 1997 and 2010. In both, low rates of perinatal transmission were reported for those periods – between 0.5% and 1.9% – with the rate falling over time.

In the 2009 recommendation, the USPSTF found adequate evidence that serologic testing for hepatitis B surface antigen accurately identifies HBV infection, and that interventions were effective in preventing perinatal transmission. That recommendation has been reaffirmed in the current update, with HBV screening receiving a grade of A, which is the strongest the USPSTF offers.

In a related editorial, Neil S. Silverman, MD, of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles noted several improvements in maternal HBV therapy since the publication of the original 2009 recommendation, including maternal HBV-targeted antiviral therapy during pregnancy as an adjunct to neonatal immunoprophylaxis and the ability to refer women for chronic treatment of their HBV disease to prevent long-term infection complications. The task forces also noted that HBV screening of all pregnant women is mandated by law in 26 states.

One member of the task force reported receiving grants and/or personal fees from Healthwise, another member reported receiving personal fees from UpToDate; a third reported participating in the American Association for the Study of Liver Diseases’ Hepatitis B Guidance and Hepatitis B Systematic Review Group. The evidence and review study was funded by the Agency for Healthcare Research and Quality. Dr. Silverman reported no disclosures.

lfranki@mdedge.com

SOURCes: Owens DK et al. JAMA. 2019 Jul 23. doi: 10.1001/jama.2019.9365; Henderson JT et al. JAMA. 2019 Jul 23;32(4):360-2; Silverman NS. JAMA. 2019 Jul 23;32(4):312-14.

The U.S. Preventive Services Task Force has updated and reaffirmed its 2009 recommendation for screening for hepatitis B virus (HBV) infection in pregnant women, according to task force member Douglas K. Owens, MD, of the Veterans Affairs Palo Alto (Calif.) Health Care System and other members of the task force.

CDC/Dr. Erskine Palmer

The recommendation statement, published in JAMA, was based on an evidence report and systematic review also published in JAMA. In that review, two studies of fair quality were identified; one included 155,081 infants born to HBV-positive women identified for case management through the national Perinatal Hepatitis B Prevention Program from 1994 to 2008, and the other included 4,446 infants born in a large, regional health care organization in the United States between 1997 and 2010. In both, low rates of perinatal transmission were reported for those periods – between 0.5% and 1.9% – with the rate falling over time.

In the 2009 recommendation, the USPSTF found adequate evidence that serologic testing for hepatitis B surface antigen accurately identifies HBV infection, and that interventions were effective in preventing perinatal transmission. That recommendation has been reaffirmed in the current update, with HBV screening receiving a grade of A, which is the strongest the USPSTF offers.

In a related editorial, Neil S. Silverman, MD, of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles noted several improvements in maternal HBV therapy since the publication of the original 2009 recommendation, including maternal HBV-targeted antiviral therapy during pregnancy as an adjunct to neonatal immunoprophylaxis and the ability to refer women for chronic treatment of their HBV disease to prevent long-term infection complications. The task forces also noted that HBV screening of all pregnant women is mandated by law in 26 states.

One member of the task force reported receiving grants and/or personal fees from Healthwise, another member reported receiving personal fees from UpToDate; a third reported participating in the American Association for the Study of Liver Diseases’ Hepatitis B Guidance and Hepatitis B Systematic Review Group. The evidence and review study was funded by the Agency for Healthcare Research and Quality. Dr. Silverman reported no disclosures.

lfranki@mdedge.com

SOURCes: Owens DK et al. JAMA. 2019 Jul 23. doi: 10.1001/jama.2019.9365; Henderson JT et al. JAMA. 2019 Jul 23;32(4):360-2; Silverman NS. JAMA. 2019 Jul 23;32(4):312-14.

To the Editor:

First documented in 1904,¹ solar urticaria is an IgE-induced condition that predominantly occurs in women aged 20 to 50 years. Worldwide prevalence and incidence information is lacking, but it is known to occur in up to 0.4% of urticaria cases.² Solar urticaria is characterized by pruritus of the skin with erythematous wheals and flares in reaction to sunlight exposure, even despite partial protection by barriers such as glass or clothing.^2,3 It can have an acute or chronic presentation caused by visible or UV light wavelengths. Solar urticaria can lead to debilitating symptoms and psychological stressors that can severely impact a patient’s well-being and also may be accompanied by conditions such as polymorphous light eruption, angioedema, or vasculitis.⁴ Standard treatments include first- and second-generation antihistamines, which are efficacious approximately 50% of the time, as well as phototherapy, which can be time consuming and a burden on patients who work or go to school full time.² Other possible treatment modalities include plasmapheresis, intravenous immunoglobulins, steroids, cyclosporine, and anti-IgE recombinant monoclonal antibody injections.^5,6 We present the case of a patient who was successfully treated with subcutaneous injections of omalizumab every 3 weeks to add to the growing number of case reports of treatment of solar urticaria.

A 30-year-old woman with Fitzpatrick skin type III and a 9-year history of solar urticaria was referred to the Department of Allergy and Immunology by her primary care physician. The patient reported that redness, swelling, and itching would occur on sun-exposed areas of the skin after approximately 10 minutes of exposure despite daily sunscreen application. She had been successfully treated with hydroxychloroquine 400 mg once daily after her first formal evaluation by dermatology 4 years prior to the current presentation. She subsequently self-discontinued treatment after 8 months of treatment due to resolution of symptoms. She noted the symptoms had returned upon relocating to Hawaii after living in the continental United States and Italy. Initially she was restarted on hydroxychloroquine 200 mg once daily and 4-times the recommended daily dose of second-generation antihistamines without relief. The hydroxychloroquine dosage subsequently was increased to 400 mg once daily, but her symptoms did not resolve.

On physical examination, sun-exposed areas of the skin showed marked macular erythema with discrete erythematous lines of demarcation observed between exposed and unexposed skin. The patient also reported concomitant pruritus, which antihistamines did not alleviate. A maximum 1-year course of cyclosporine 300 mg once daily initially was planned but was discontinued due to immediate onset of severe nausea and emesis after the first dose as well as continued outbreaks of urticaria for 1 month after incrementally increasing by 100 mg from a starting dose of 100 mg.

After discussion with the dermatology department, a trial of omalizumab was started because the daily impact of a UV light sensitization course was not feasible with her work schedule, and serum IgE blood level was 560.4 µg/L (reference range, 0–1500 µg/L). The patient was started on a regimen of omalizumab 300 mg (subcutaneous injections) every 2 weeks with noted improvement after the third dose, with no urticarial symptoms after sun exposure. After 2 months, the dosage interval was increased to every 4 weeks given her level of improvement, but her symptoms recurred. The treatment regimen was then changed to every 3 weeks. The patient was symptom free for a period of 10 months on this regimen, followed by only 1 outbreak of erythema and urticaria, which occurred 1 day prior to a scheduled omalizumab injection. Symptoms have otherwise been well controlled to date on omalizumab.

Solar urticaria is a poorly understood phenomenon that has no clear prognostic indicators; therefore, diagnosis often is made based on the patient’s history and physical examination. Further testing to confirm the diagnosis can be performed using specific wavelengths of UV light to determine which band of light affects patients most; however, the wavelength can change over time, leading to less clinical significance, and may decrease efficacy of phototherapy.² Solar urticaria has no clear predisposing factors, and treatments to date have been moderately successful. Exposure to sunlight is thought to initiate an alteration in a skin or serum chromophore or photoallergen, which then causes subsequent cross-linking and IgE-dependent release of histamine as well as other mediators such as cytokines, eicosanoids, and proteases with mast cell degranulation.⁷

Omalizumab is a recombinant humanized monoclonal IgG1 antibody targeting the methylated IgE Cε3 domain that initially was marketed toward controlling IgE-mediated moderate to severe asthma recalcitrant to standard treatments. It has since received approval from the US Food and Drug Administration for treatment of chronic idiopathic urticaria after first being noticed to serendipitously treat a patient with cold urticaria and asthma in 2006.^4,7,8 It was then first documented to successfully treat solar urticaria in 2008.⁶ The safety profile of omalizumab makes it a more favorable choice when compared to other immunomodulating treatments, with the most serious adverse reaction being anaphylaxis, occurring in 0.2% of patients in a postmarketing study.⁹ It functions through binding to free IgE at a region necessary for IgE to bind at low- and high-affinity receptors but not to immunoglobulins already bound to cells, thus theoretically preventing activation of mast cells or basophils.¹⁰ It also has been suggested that low steady-state values are needed to see continued benefit from the drug,¹⁰ which may have been seen in our patient after having an outbreak just prior to receiving an injection; however, prior reports have shown benefit unrelated to total IgE levels, with improvement after days to 4 months.^4,10,11 One case report showed no response after 4 doses; it is unknown if this patient was tested for clinical improvement to omalizumab through further immunoglobulin analysis, but treatment response is important to consider when deciding on whether to use this drug in future patients.¹² It is unknown why some patients will respond to omalizumab, others will partially respond, and others will not respond, which can be ascertained either through quality-of-life improvement or lack thereof.

In our experience, omalizumab is a viable option to consider in patients with solar urticaria that is recalcitrant to standard treatments and elevated IgE levels for whom other treatments are either too time consuming or have side-effect profiles that are not tolerable to the patient. If the patient has concomitant asthma, there may be additional therapeutic benefit. Further research is needed with regard to a cost-benefit analysis of omalizumab and whether using such a costly drug outweighs the cost associated with time and resources utilized with repeat clinic visits if other standard treatments are not effective.¹³

To the Editor:

First documented in 1904,¹ solar urticaria is an IgE-induced condition that predominantly occurs in women aged 20 to 50 years. Worldwide prevalence and incidence information is lacking, but it is known to occur in up to 0.4% of urticaria cases.² Solar urticaria is characterized by pruritus of the skin with erythematous wheals and flares in reaction to sunlight exposure, even despite partial protection by barriers such as glass or clothing.^2,3 It can have an acute or chronic presentation caused by visible or UV light wavelengths. Solar urticaria can lead to debilitating symptoms and psychological stressors that can severely impact a patient’s well-being and also may be accompanied by conditions such as polymorphous light eruption, angioedema, or vasculitis.⁴ Standard treatments include first- and second-generation antihistamines, which are efficacious approximately 50% of the time, as well as phototherapy, which can be time consuming and a burden on patients who work or go to school full time.² Other possible treatment modalities include plasmapheresis, intravenous immunoglobulins, steroids, cyclosporine, and anti-IgE recombinant monoclonal antibody injections.^5,6 We present the case of a patient who was successfully treated with subcutaneous injections of omalizumab every 3 weeks to add to the growing number of case reports of treatment of solar urticaria.

A 30-year-old woman with Fitzpatrick skin type III and a 9-year history of solar urticaria was referred to the Department of Allergy and Immunology by her primary care physician. The patient reported that redness, swelling, and itching would occur on sun-exposed areas of the skin after approximately 10 minutes of exposure despite daily sunscreen application. She had been successfully treated with hydroxychloroquine 400 mg once daily after her first formal evaluation by dermatology 4 years prior to the current presentation. She subsequently self-discontinued treatment after 8 months of treatment due to resolution of symptoms. She noted the symptoms had returned upon relocating to Hawaii after living in the continental United States and Italy. Initially she was restarted on hydroxychloroquine 200 mg once daily and 4-times the recommended daily dose of second-generation antihistamines without relief. The hydroxychloroquine dosage subsequently was increased to 400 mg once daily, but her symptoms did not resolve.

On physical examination, sun-exposed areas of the skin showed marked macular erythema with discrete erythematous lines of demarcation observed between exposed and unexposed skin. The patient also reported concomitant pruritus, which antihistamines did not alleviate. A maximum 1-year course of cyclosporine 300 mg once daily initially was planned but was discontinued due to immediate onset of severe nausea and emesis after the first dose as well as continued outbreaks of urticaria for 1 month after incrementally increasing by 100 mg from a starting dose of 100 mg.

After discussion with the dermatology department, a trial of omalizumab was started because the daily impact of a UV light sensitization course was not feasible with her work schedule, and serum IgE blood level was 560.4 µg/L (reference range, 0–1500 µg/L). The patient was started on a regimen of omalizumab 300 mg (subcutaneous injections) every 2 weeks with noted improvement after the third dose, with no urticarial symptoms after sun exposure. After 2 months, the dosage interval was increased to every 4 weeks given her level of improvement, but her symptoms recurred. The treatment regimen was then changed to every 3 weeks. The patient was symptom free for a period of 10 months on this regimen, followed by only 1 outbreak of erythema and urticaria, which occurred 1 day prior to a scheduled omalizumab injection. Symptoms have otherwise been well controlled to date on omalizumab.

Solar urticaria is a poorly understood phenomenon that has no clear prognostic indicators; therefore, diagnosis often is made based on the patient’s history and physical examination. Further testing to confirm the diagnosis can be performed using specific wavelengths of UV light to determine which band of light affects patients most; however, the wavelength can change over time, leading to less clinical significance, and may decrease efficacy of phototherapy.² Solar urticaria has no clear predisposing factors, and treatments to date have been moderately successful. Exposure to sunlight is thought to initiate an alteration in a skin or serum chromophore or photoallergen, which then causes subsequent cross-linking and IgE-dependent release of histamine as well as other mediators such as cytokines, eicosanoids, and proteases with mast cell degranulation.⁷

Omalizumab is a recombinant humanized monoclonal IgG1 antibody targeting the methylated IgE Cε3 domain that initially was marketed toward controlling IgE-mediated moderate to severe asthma recalcitrant to standard treatments. It has since received approval from the US Food and Drug Administration for treatment of chronic idiopathic urticaria after first being noticed to serendipitously treat a patient with cold urticaria and asthma in 2006.^4,7,8 It was then first documented to successfully treat solar urticaria in 2008.⁶ The safety profile of omalizumab makes it a more favorable choice when compared to other immunomodulating treatments, with the most serious adverse reaction being anaphylaxis, occurring in 0.2% of patients in a postmarketing study.⁹ It functions through binding to free IgE at a region necessary for IgE to bind at low- and high-affinity receptors but not to immunoglobulins already bound to cells, thus theoretically preventing activation of mast cells or basophils.¹⁰ It also has been suggested that low steady-state values are needed to see continued benefit from the drug,¹⁰ which may have been seen in our patient after having an outbreak just prior to receiving an injection; however, prior reports have shown benefit unrelated to total IgE levels, with improvement after days to 4 months.^4,10,11 One case report showed no response after 4 doses; it is unknown if this patient was tested for clinical improvement to omalizumab through further immunoglobulin analysis, but treatment response is important to consider when deciding on whether to use this drug in future patients.¹² It is unknown why some patients will respond to omalizumab, others will partially respond, and others will not respond, which can be ascertained either through quality-of-life improvement or lack thereof.

In our experience, omalizumab is a viable option to consider in patients with solar urticaria that is recalcitrant to standard treatments and elevated IgE levels for whom other treatments are either too time consuming or have side-effect profiles that are not tolerable to the patient. If the patient has concomitant asthma, there may be additional therapeutic benefit. Further research is needed with regard to a cost-benefit analysis of omalizumab and whether using such a costly drug outweighs the cost associated with time and resources utilized with repeat clinic visits if other standard treatments are not effective.¹³

To the Editor:

First documented in 1904,¹ solar urticaria is an IgE-induced condition that predominantly occurs in women aged 20 to 50 years. Worldwide prevalence and incidence information is lacking, but it is known to occur in up to 0.4% of urticaria cases.² Solar urticaria is characterized by pruritus of the skin with erythematous wheals and flares in reaction to sunlight exposure, even despite partial protection by barriers such as glass or clothing.^2,3 It can have an acute or chronic presentation caused by visible or UV light wavelengths. Solar urticaria can lead to debilitating symptoms and psychological stressors that can severely impact a patient’s well-being and also may be accompanied by conditions such as polymorphous light eruption, angioedema, or vasculitis.⁴ Standard treatments include first- and second-generation antihistamines, which are efficacious approximately 50% of the time, as well as phototherapy, which can be time consuming and a burden on patients who work or go to school full time.² Other possible treatment modalities include plasmapheresis, intravenous immunoglobulins, steroids, cyclosporine, and anti-IgE recombinant monoclonal antibody injections.^5,6 We present the case of a patient who was successfully treated with subcutaneous injections of omalizumab every 3 weeks to add to the growing number of case reports of treatment of solar urticaria.

A 30-year-old woman with Fitzpatrick skin type III and a 9-year history of solar urticaria was referred to the Department of Allergy and Immunology by her primary care physician. The patient reported that redness, swelling, and itching would occur on sun-exposed areas of the skin after approximately 10 minutes of exposure despite daily sunscreen application. She had been successfully treated with hydroxychloroquine 400 mg once daily after her first formal evaluation by dermatology 4 years prior to the current presentation. She subsequently self-discontinued treatment after 8 months of treatment due to resolution of symptoms. She noted the symptoms had returned upon relocating to Hawaii after living in the continental United States and Italy. Initially she was restarted on hydroxychloroquine 200 mg once daily and 4-times the recommended daily dose of second-generation antihistamines without relief. The hydroxychloroquine dosage subsequently was increased to 400 mg once daily, but her symptoms did not resolve.

On physical examination, sun-exposed areas of the skin showed marked macular erythema with discrete erythematous lines of demarcation observed between exposed and unexposed skin. The patient also reported concomitant pruritus, which antihistamines did not alleviate. A maximum 1-year course of cyclosporine 300 mg once daily initially was planned but was discontinued due to immediate onset of severe nausea and emesis after the first dose as well as continued outbreaks of urticaria for 1 month after incrementally increasing by 100 mg from a starting dose of 100 mg.

After discussion with the dermatology department, a trial of omalizumab was started because the daily impact of a UV light sensitization course was not feasible with her work schedule, and serum IgE blood level was 560.4 µg/L (reference range, 0–1500 µg/L). The patient was started on a regimen of omalizumab 300 mg (subcutaneous injections) every 2 weeks with noted improvement after the third dose, with no urticarial symptoms after sun exposure. After 2 months, the dosage interval was increased to every 4 weeks given her level of improvement, but her symptoms recurred. The treatment regimen was then changed to every 3 weeks. The patient was symptom free for a period of 10 months on this regimen, followed by only 1 outbreak of erythema and urticaria, which occurred 1 day prior to a scheduled omalizumab injection. Symptoms have otherwise been well controlled to date on omalizumab.

Solar urticaria is a poorly understood phenomenon that has no clear prognostic indicators; therefore, diagnosis often is made based on the patient’s history and physical examination. Further testing to confirm the diagnosis can be performed using specific wavelengths of UV light to determine which band of light affects patients most; however, the wavelength can change over time, leading to less clinical significance, and may decrease efficacy of phototherapy.² Solar urticaria has no clear predisposing factors, and treatments to date have been moderately successful. Exposure to sunlight is thought to initiate an alteration in a skin or serum chromophore or photoallergen, which then causes subsequent cross-linking and IgE-dependent release of histamine as well as other mediators such as cytokines, eicosanoids, and proteases with mast cell degranulation.⁷

Omalizumab is a recombinant humanized monoclonal IgG1 antibody targeting the methylated IgE Cε3 domain that initially was marketed toward controlling IgE-mediated moderate to severe asthma recalcitrant to standard treatments. It has since received approval from the US Food and Drug Administration for treatment of chronic idiopathic urticaria after first being noticed to serendipitously treat a patient with cold urticaria and asthma in 2006.^4,7,8 It was then first documented to successfully treat solar urticaria in 2008.⁶ The safety profile of omalizumab makes it a more favorable choice when compared to other immunomodulating treatments, with the most serious adverse reaction being anaphylaxis, occurring in 0.2% of patients in a postmarketing study.⁹ It functions through binding to free IgE at a region necessary for IgE to bind at low- and high-affinity receptors but not to immunoglobulins already bound to cells, thus theoretically preventing activation of mast cells or basophils.¹⁰ It also has been suggested that low steady-state values are needed to see continued benefit from the drug,¹⁰ which may have been seen in our patient after having an outbreak just prior to receiving an injection; however, prior reports have shown benefit unrelated to total IgE levels, with improvement after days to 4 months.^4,10,11 One case report showed no response after 4 doses; it is unknown if this patient was tested for clinical improvement to omalizumab through further immunoglobulin analysis, but treatment response is important to consider when deciding on whether to use this drug in future patients.¹² It is unknown why some patients will respond to omalizumab, others will partially respond, and others will not respond, which can be ascertained either through quality-of-life improvement or lack thereof.

In our experience, omalizumab is a viable option to consider in patients with solar urticaria that is recalcitrant to standard treatments and elevated IgE levels for whom other treatments are either too time consuming or have side-effect profiles that are not tolerable to the patient. If the patient has concomitant asthma, there may be additional therapeutic benefit. Further research is needed with regard to a cost-benefit analysis of omalizumab and whether using such a costly drug outweighs the cost associated with time and resources utilized with repeat clinic visits if other standard treatments are not effective.¹³