Roxanne Nelson

For men with hormone-sensitive metastatic prostate cancer, combining standard androgen deprivation therapy with six cycles of docetaxel resulted in a significantly longer overall survival, compared with standard ADT alone, according to a study published online in the New England Journal of Medicine.

Men who received the combination therapy had “better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival,” wrote Dr. Christopher J. Sweeney of the Dana Farber Cancer Institute, Boston, and his colleagues (N Engl J Med. 2015 Aug 5. doi: 10.1056/NEJMoa1503747).

roobcio/Thinkstock.com

Investigators sought to find out whether docetaxel therapy given at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in a longer overall survival than with ADT alone, even though previous studies of chemotherapy plus ADT did not show a benefit. However, the researchers noted that these were small studies that primarily included patients with a relatively low tumor burden.

The study included 790 men with metastatic hormone sensitive prostate cancer, with a median age of 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 70% had an ECOG performance-status score of 0, 65% had high-volume disease, and 60% had a Gleason score of 8 or higher. In both cohorts, 73% had received no prior therapy with a curative intent.

The median overall survival was 13.6 months longer in the group receiving ADT and docetaxel, compared with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P less than.001).

There were 85 prostate cancer deaths in the combination therapy group, compared with 114 prostate cancer deaths in the ADT-alone group.

The addition of docetaxel to the regimen appeared to benefit all subgroups analyzed, although the median survival at the time of the analysis had not been reached in the subgroup with low-volume disease, in either of the two groups.

The “benefit at the last analysis was more apparent in the subgroup with high-volume disease than in the overall study population,” noted Dr. Sweeney and colleagues. Median overall survival was 17.0 months longer in the combination group than in the ADT-alone group (49.2 months vs.32.2 months; HR for death, 0.60; 95% CI, 0.45 to 0.81; P less than.001).

As for secondary endpoints, the proportion of patients who showed a decline in the PSA level to less than 0.2 ng/mL at 12 months was higher in the combination therapy group: 27.7% compared with 16.8% in the ADT-alone group (P less than.001).

The median time to the development of castration-resistant prostate cancer (biochemical, symptomatic, or radiographic) was also longer in the combination therapy group (20.2 months vs 11.7 months; HR 0.61; 95% CI, 0.51 to 0.72; P less than.001), as was median time to clinical progression (33.0 months vs 19.8 months, HR, 0.61; 95% CI, 0.50 to 0.75; P less than.001).

The addition of docetaxel was associated with higher toxicity. In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, grade 3 or 4 infection with neutropenia was 2.3%, and approximately 1% of the patients had a thromboembolic event.

For men with hormone-sensitive metastatic prostate cancer, combining standard androgen deprivation therapy with six cycles of docetaxel resulted in a significantly longer overall survival, compared with standard ADT alone, according to a study published online in the New England Journal of Medicine.

Men who received the combination therapy had “better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival,” wrote Dr. Christopher J. Sweeney of the Dana Farber Cancer Institute, Boston, and his colleagues (N Engl J Med. 2015 Aug 5. doi: 10.1056/NEJMoa1503747).

roobcio/Thinkstock.com

Investigators sought to find out whether docetaxel therapy given at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in a longer overall survival than with ADT alone, even though previous studies of chemotherapy plus ADT did not show a benefit. However, the researchers noted that these were small studies that primarily included patients with a relatively low tumor burden.

The study included 790 men with metastatic hormone sensitive prostate cancer, with a median age of 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 70% had an ECOG performance-status score of 0, 65% had high-volume disease, and 60% had a Gleason score of 8 or higher. In both cohorts, 73% had received no prior therapy with a curative intent.

The median overall survival was 13.6 months longer in the group receiving ADT and docetaxel, compared with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P less than.001).

There were 85 prostate cancer deaths in the combination therapy group, compared with 114 prostate cancer deaths in the ADT-alone group.

The addition of docetaxel to the regimen appeared to benefit all subgroups analyzed, although the median survival at the time of the analysis had not been reached in the subgroup with low-volume disease, in either of the two groups.

The “benefit at the last analysis was more apparent in the subgroup with high-volume disease than in the overall study population,” noted Dr. Sweeney and colleagues. Median overall survival was 17.0 months longer in the combination group than in the ADT-alone group (49.2 months vs.32.2 months; HR for death, 0.60; 95% CI, 0.45 to 0.81; P less than.001).

As for secondary endpoints, the proportion of patients who showed a decline in the PSA level to less than 0.2 ng/mL at 12 months was higher in the combination therapy group: 27.7% compared with 16.8% in the ADT-alone group (P less than.001).

The median time to the development of castration-resistant prostate cancer (biochemical, symptomatic, or radiographic) was also longer in the combination therapy group (20.2 months vs 11.7 months; HR 0.61; 95% CI, 0.51 to 0.72; P less than.001), as was median time to clinical progression (33.0 months vs 19.8 months, HR, 0.61; 95% CI, 0.50 to 0.75; P less than.001).

The addition of docetaxel was associated with higher toxicity. In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, grade 3 or 4 infection with neutropenia was 2.3%, and approximately 1% of the patients had a thromboembolic event.

For men with hormone-sensitive metastatic prostate cancer, combining standard androgen deprivation therapy with six cycles of docetaxel resulted in a significantly longer overall survival, compared with standard ADT alone, according to a study published online in the New England Journal of Medicine.

Men who received the combination therapy had “better cancer control than that with ADT alone, with a longer time to the development of castration resistance, a higher rate of decrease of the PSA level to less than 0.2 ng per milliliter at 12 months, a lower number of prostate-cancer deaths, and substantially longer overall survival,” wrote Dr. Christopher J. Sweeney of the Dana Farber Cancer Institute, Boston, and his colleagues (N Engl J Med. 2015 Aug 5. doi: 10.1056/NEJMoa1503747).

roobcio/Thinkstock.com

Investigators sought to find out whether docetaxel therapy given at the beginning of ADT for metastatic hormone-sensitive prostate cancer would result in a longer overall survival than with ADT alone, even though previous studies of chemotherapy plus ADT did not show a benefit. However, the researchers noted that these were small studies that primarily included patients with a relatively low tumor burden.

The study included 790 men with metastatic hormone sensitive prostate cancer, with a median age of 64 years (range, 36 to 88) in the combination group and 63 years (range, 39 to 91) in the ADT-alone group. In both groups, approximately 70% had an ECOG performance-status score of 0, 65% had high-volume disease, and 60% had a Gleason score of 8 or higher. In both cohorts, 73% had received no prior therapy with a curative intent.

The median overall survival was 13.6 months longer in the group receiving ADT and docetaxel, compared with ADT alone (57.6 months vs. 44.0 months; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI], 0.47 to 0.80; P less than.001).

There were 85 prostate cancer deaths in the combination therapy group, compared with 114 prostate cancer deaths in the ADT-alone group.

The addition of docetaxel to the regimen appeared to benefit all subgroups analyzed, although the median survival at the time of the analysis had not been reached in the subgroup with low-volume disease, in either of the two groups.

The “benefit at the last analysis was more apparent in the subgroup with high-volume disease than in the overall study population,” noted Dr. Sweeney and colleagues. Median overall survival was 17.0 months longer in the combination group than in the ADT-alone group (49.2 months vs.32.2 months; HR for death, 0.60; 95% CI, 0.45 to 0.81; P less than.001).

As for secondary endpoints, the proportion of patients who showed a decline in the PSA level to less than 0.2 ng/mL at 12 months was higher in the combination therapy group: 27.7% compared with 16.8% in the ADT-alone group (P less than.001).

The median time to the development of castration-resistant prostate cancer (biochemical, symptomatic, or radiographic) was also longer in the combination therapy group (20.2 months vs 11.7 months; HR 0.61; 95% CI, 0.51 to 0.72; P less than.001), as was median time to clinical progression (33.0 months vs 19.8 months, HR, 0.61; 95% CI, 0.50 to 0.75; P less than.001).

The addition of docetaxel was associated with higher toxicity. In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, grade 3 or 4 infection with neutropenia was 2.3%, and approximately 1% of the patients had a thromboembolic event.

A single tool that combines the International Staging System (ISS) with testing for chromosomal abnormalities (CA) and serum lactate dehydrogenase (LDH) affords a superior staging system for multiple myeloma, according to a study published in the Journal of Clinical Oncology.

The new staging system, called R-ISS, was able to identify three survival patterns in patients with newly diagnosed multiple myeloma:

• The first, R-ISS I (n = 871), included ISS stage I (serum 2-microglobulin level less than 3.5 mg/L and serum albumin level of 3.5 g/dL or more), no high-risk chromosomal abnormalities [del(17p) and/or t(4;14) and/or t(14;16)], and normal serum lactate dehydrogenase level (less than the upper limit of normal range).

• R-ISS III (n = 295) included ISS stage III (serum-beta-2-microglobulin level greater than 5.5 mg/L) and high-risk chromosomal abnormalities or high serum lactate dehydrogenase level.

• R-ISS II (n = 1,894) included all other possible combinations.

Corresponding rates of 5-year overall survival were 82% for R-ISS stage I, 62% for R-ISS stage II, and 40% for R-ISS stage III at a median follow-up of 46 months. The 5-year progression-free survival rates were 55%, 36%, and 24%, respectively.

Multiple myeloma “can no longer be considered a single disease, but a mix of different disease entities,” wrote Dr. Antonio Palumbo, chief of the myeloma unit in the department of oncology, division of hematology, University of Torino (Italy) and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.2267).

“The combination of three different prognostic tools in the R-ISS allows a better evaluation of patient prognosis; approximately 26% of patients would have been wrongly allocated to a good-prognosis group if we had considered only one of these three factors,” the authors emphasized.

“In clinical practice, a better definition of [multiple myeloma] subgroups is essential to provide more effective personalized therapies,” they said. “The R-ISS staging system is a new risk stratification algorithm with an improved prognostic power compared with the individual ISS, CA, and LDH parameters.”

The individual roles of the three predictors in R-ISS were initially evaluated in a population of 4,445 patients with newly diagnosed multiple myeloma who were enrolled in 11 international, multicenter clinical trials from 2005 to 2012. The authors used the K-adaptive partitioning algorithm to define the most appropriate subgroups in 3,060 patients who had complete ISS, CA, and LDH data.

Subgroup analyses for overall survival and progression-free survival also were conducted. The risk of death was higher for patients older than 65 years (hazard ratio, 1.32; 95% confidence interval, 1.14-1.52; P <.001), male sex (HR, 1.16; 95% CI, 1.02-1.33; P = .029), R-ISS stage II versus I (HR, 3.59; 95% CI, 2.68-4.80; P <.001), and R-ISS stage III versus I (HR, 9.64; 95% CI, 6.24-14.88; P <.001).

The risk of progression also was higher for those older than 65 years (HR, 1.57; 95% CI, 1.42-1.75; P <.001), R-ISS stage II versus I (HR, 1.99; 95% CI, 1.61-2.37; P <.001), and R-ISS stage III versus I (HR, 3.37; 95% CI, 2.54-4.56; P <.001).

Almost all (95%) of the patients received novel agents, and these therapies improved overall survival across prognostic subgroups.

There is no disclosure of outside funding for this study. Several of the coauthors have disclosed financial relationships with industry, as noted in the paper.

A single tool that combines the International Staging System (ISS) with testing for chromosomal abnormalities (CA) and serum lactate dehydrogenase (LDH) affords a superior staging system for multiple myeloma, according to a study published in the Journal of Clinical Oncology.

The new staging system, called R-ISS, was able to identify three survival patterns in patients with newly diagnosed multiple myeloma:

• The first, R-ISS I (n = 871), included ISS stage I (serum 2-microglobulin level less than 3.5 mg/L and serum albumin level of 3.5 g/dL or more), no high-risk chromosomal abnormalities [del(17p) and/or t(4;14) and/or t(14;16)], and normal serum lactate dehydrogenase level (less than the upper limit of normal range).

• R-ISS III (n = 295) included ISS stage III (serum-beta-2-microglobulin level greater than 5.5 mg/L) and high-risk chromosomal abnormalities or high serum lactate dehydrogenase level.

• R-ISS II (n = 1,894) included all other possible combinations.

Corresponding rates of 5-year overall survival were 82% for R-ISS stage I, 62% for R-ISS stage II, and 40% for R-ISS stage III at a median follow-up of 46 months. The 5-year progression-free survival rates were 55%, 36%, and 24%, respectively.

Multiple myeloma “can no longer be considered a single disease, but a mix of different disease entities,” wrote Dr. Antonio Palumbo, chief of the myeloma unit in the department of oncology, division of hematology, University of Torino (Italy) and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.2267).

“The combination of three different prognostic tools in the R-ISS allows a better evaluation of patient prognosis; approximately 26% of patients would have been wrongly allocated to a good-prognosis group if we had considered only one of these three factors,” the authors emphasized.

“In clinical practice, a better definition of [multiple myeloma] subgroups is essential to provide more effective personalized therapies,” they said. “The R-ISS staging system is a new risk stratification algorithm with an improved prognostic power compared with the individual ISS, CA, and LDH parameters.”

The individual roles of the three predictors in R-ISS were initially evaluated in a population of 4,445 patients with newly diagnosed multiple myeloma who were enrolled in 11 international, multicenter clinical trials from 2005 to 2012. The authors used the K-adaptive partitioning algorithm to define the most appropriate subgroups in 3,060 patients who had complete ISS, CA, and LDH data.

Subgroup analyses for overall survival and progression-free survival also were conducted. The risk of death was higher for patients older than 65 years (hazard ratio, 1.32; 95% confidence interval, 1.14-1.52; P <.001), male sex (HR, 1.16; 95% CI, 1.02-1.33; P = .029), R-ISS stage II versus I (HR, 3.59; 95% CI, 2.68-4.80; P <.001), and R-ISS stage III versus I (HR, 9.64; 95% CI, 6.24-14.88; P <.001).

The risk of progression also was higher for those older than 65 years (HR, 1.57; 95% CI, 1.42-1.75; P <.001), R-ISS stage II versus I (HR, 1.99; 95% CI, 1.61-2.37; P <.001), and R-ISS stage III versus I (HR, 3.37; 95% CI, 2.54-4.56; P <.001).

Almost all (95%) of the patients received novel agents, and these therapies improved overall survival across prognostic subgroups.

There is no disclosure of outside funding for this study. Several of the coauthors have disclosed financial relationships with industry, as noted in the paper.

A single tool that combines the International Staging System (ISS) with testing for chromosomal abnormalities (CA) and serum lactate dehydrogenase (LDH) affords a superior staging system for multiple myeloma, according to a study published in the Journal of Clinical Oncology.

The new staging system, called R-ISS, was able to identify three survival patterns in patients with newly diagnosed multiple myeloma:

• The first, R-ISS I (n = 871), included ISS stage I (serum 2-microglobulin level less than 3.5 mg/L and serum albumin level of 3.5 g/dL or more), no high-risk chromosomal abnormalities [del(17p) and/or t(4;14) and/or t(14;16)], and normal serum lactate dehydrogenase level (less than the upper limit of normal range).

• R-ISS III (n = 295) included ISS stage III (serum-beta-2-microglobulin level greater than 5.5 mg/L) and high-risk chromosomal abnormalities or high serum lactate dehydrogenase level.

• R-ISS II (n = 1,894) included all other possible combinations.

Corresponding rates of 5-year overall survival were 82% for R-ISS stage I, 62% for R-ISS stage II, and 40% for R-ISS stage III at a median follow-up of 46 months. The 5-year progression-free survival rates were 55%, 36%, and 24%, respectively.

Multiple myeloma “can no longer be considered a single disease, but a mix of different disease entities,” wrote Dr. Antonio Palumbo, chief of the myeloma unit in the department of oncology, division of hematology, University of Torino (Italy) and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2015.61.2267).

“The combination of three different prognostic tools in the R-ISS allows a better evaluation of patient prognosis; approximately 26% of patients would have been wrongly allocated to a good-prognosis group if we had considered only one of these three factors,” the authors emphasized.

“In clinical practice, a better definition of [multiple myeloma] subgroups is essential to provide more effective personalized therapies,” they said. “The R-ISS staging system is a new risk stratification algorithm with an improved prognostic power compared with the individual ISS, CA, and LDH parameters.”

The individual roles of the three predictors in R-ISS were initially evaluated in a population of 4,445 patients with newly diagnosed multiple myeloma who were enrolled in 11 international, multicenter clinical trials from 2005 to 2012. The authors used the K-adaptive partitioning algorithm to define the most appropriate subgroups in 3,060 patients who had complete ISS, CA, and LDH data.

Subgroup analyses for overall survival and progression-free survival also were conducted. The risk of death was higher for patients older than 65 years (hazard ratio, 1.32; 95% confidence interval, 1.14-1.52; P <.001), male sex (HR, 1.16; 95% CI, 1.02-1.33; P = .029), R-ISS stage II versus I (HR, 3.59; 95% CI, 2.68-4.80; P <.001), and R-ISS stage III versus I (HR, 9.64; 95% CI, 6.24-14.88; P <.001).

The risk of progression also was higher for those older than 65 years (HR, 1.57; 95% CI, 1.42-1.75; P <.001), R-ISS stage II versus I (HR, 1.99; 95% CI, 1.61-2.37; P <.001), and R-ISS stage III versus I (HR, 3.37; 95% CI, 2.54-4.56; P <.001).

Almost all (95%) of the patients received novel agents, and these therapies improved overall survival across prognostic subgroups.

There is no disclosure of outside funding for this study. Several of the coauthors have disclosed financial relationships with industry, as noted in the paper.

The American Society of Clinical Oncology has issued updated guidelines on using breast tumor biomarker assays to help guide or influence decisions on systemic therapy in women with metastatic breast cancer, which were published online July 20 in the Journal of Clinical Oncology.

The quality of evidence for the recommendations ranges from insufficient to intermediate, and the “strength” of the recommendation was moderate for all of them.

When evaluating metastatic sites, it is important to note that the estrogen receptor (ER), progesterone receptor (PR), and/or human epidermal growth factor receptor 2 (HER2) status may have changed from the primary tumor, and these results could influence treatment. Thus, biopsy should be offered to patients with accessible, newly diagnosed metastases from primary breast cancer, to confirm disease status and test for ER, PR, and HER2 status, wrote Dr. Catherine Van Poznak of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues, as one of the key recommendations (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.1459]).

Patients should be also be told if discordances are detected, and that evidence is lacking to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor.

If supported by the clinical scenario and patient goals for care, the ASCO Panel consensus is to preferentially use the biomarker status from the metastatic site rather than from the primary tumor, to direct therapy.

Decisions for initiating systemic therapy in this patient population should be based on clinical evaluation, judgment, as well as patient preferences. At present, there is no evidence that health outcomes will improve if treatment is initiated based solely on the results of biomarker assays that go beyond ER, PR, and HER2 status.

For patients who are already receiving systemic therapy, decisions for changing drugs or regimens, or discontinuing treatment should be based on clinical evaluation, clinician judgment of disease progression or response, and patient preference and input. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness, they wrote. This recommendation applies for both tissue biomarkers and circulating tumor biomarkers.

The guidelines also recommend that carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 can be used as adjunctive assessments and can contribute to decisions regarding therapy. The data thus far, however, are insufficient to recommend their use alone for monitoring response to treatment. This recommendation, according to the researchers, is based on clinical experience and the informal consensus of the panel, since there are no studies that have been designed to evaluate the clinical utility of the markers.

It is also reasonable for clinicians to not use these markers as adjunctive assessments.

Outside of clinical trials, decisions for systemic therapy should be influenced by ER, PR, and HER2 status, as the clinical usefulness for other biomarkers has not yet been demonstrated. A number of other types of biomarkers are in active development, but there is insufficient evidence at this time showing that their use improves cancer outcomes, the panel said.

Biomarker distribution of ER, PR, and HER2 status may also differ across ethnic and racial backgrounds, and in addition to the biologic variability of these biomarkers, there is also evidence that disparities exist in the frequency of biomarker testing in certain populations.

The American Society of Clinical Oncology has issued updated guidelines on using breast tumor biomarker assays to help guide or influence decisions on systemic therapy in women with metastatic breast cancer, which were published online July 20 in the Journal of Clinical Oncology.

The quality of evidence for the recommendations ranges from insufficient to intermediate, and the “strength” of the recommendation was moderate for all of them.

When evaluating metastatic sites, it is important to note that the estrogen receptor (ER), progesterone receptor (PR), and/or human epidermal growth factor receptor 2 (HER2) status may have changed from the primary tumor, and these results could influence treatment. Thus, biopsy should be offered to patients with accessible, newly diagnosed metastases from primary breast cancer, to confirm disease status and test for ER, PR, and HER2 status, wrote Dr. Catherine Van Poznak of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues, as one of the key recommendations (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.1459]).

Patients should be also be told if discordances are detected, and that evidence is lacking to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor.

If supported by the clinical scenario and patient goals for care, the ASCO Panel consensus is to preferentially use the biomarker status from the metastatic site rather than from the primary tumor, to direct therapy.

Decisions for initiating systemic therapy in this patient population should be based on clinical evaluation, judgment, as well as patient preferences. At present, there is no evidence that health outcomes will improve if treatment is initiated based solely on the results of biomarker assays that go beyond ER, PR, and HER2 status.

For patients who are already receiving systemic therapy, decisions for changing drugs or regimens, or discontinuing treatment should be based on clinical evaluation, clinician judgment of disease progression or response, and patient preference and input. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness, they wrote. This recommendation applies for both tissue biomarkers and circulating tumor biomarkers.

The guidelines also recommend that carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 can be used as adjunctive assessments and can contribute to decisions regarding therapy. The data thus far, however, are insufficient to recommend their use alone for monitoring response to treatment. This recommendation, according to the researchers, is based on clinical experience and the informal consensus of the panel, since there are no studies that have been designed to evaluate the clinical utility of the markers.

It is also reasonable for clinicians to not use these markers as adjunctive assessments.

Outside of clinical trials, decisions for systemic therapy should be influenced by ER, PR, and HER2 status, as the clinical usefulness for other biomarkers has not yet been demonstrated. A number of other types of biomarkers are in active development, but there is insufficient evidence at this time showing that their use improves cancer outcomes, the panel said.

Biomarker distribution of ER, PR, and HER2 status may also differ across ethnic and racial backgrounds, and in addition to the biologic variability of these biomarkers, there is also evidence that disparities exist in the frequency of biomarker testing in certain populations.

The American Society of Clinical Oncology has issued updated guidelines on using breast tumor biomarker assays to help guide or influence decisions on systemic therapy in women with metastatic breast cancer, which were published online July 20 in the Journal of Clinical Oncology.

The quality of evidence for the recommendations ranges from insufficient to intermediate, and the “strength” of the recommendation was moderate for all of them.

When evaluating metastatic sites, it is important to note that the estrogen receptor (ER), progesterone receptor (PR), and/or human epidermal growth factor receptor 2 (HER2) status may have changed from the primary tumor, and these results could influence treatment. Thus, biopsy should be offered to patients with accessible, newly diagnosed metastases from primary breast cancer, to confirm disease status and test for ER, PR, and HER2 status, wrote Dr. Catherine Van Poznak of the University of Michigan Comprehensive Cancer Center in Ann Arbor, and colleagues, as one of the key recommendations (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.1459]).

Patients should be also be told if discordances are detected, and that evidence is lacking to determine whether outcomes are better with treatment regimens based on receptor status in the metastases or the primary tumor.

If supported by the clinical scenario and patient goals for care, the ASCO Panel consensus is to preferentially use the biomarker status from the metastatic site rather than from the primary tumor, to direct therapy.

Decisions for initiating systemic therapy in this patient population should be based on clinical evaluation, judgment, as well as patient preferences. At present, there is no evidence that health outcomes will improve if treatment is initiated based solely on the results of biomarker assays that go beyond ER, PR, and HER2 status.

For patients who are already receiving systemic therapy, decisions for changing drugs or regimens, or discontinuing treatment should be based on clinical evaluation, clinician judgment of disease progression or response, and patient preference and input. There is no evidence at this time that changing therapy based solely on biomarker results beyond ER, PR, and HER2 improves health outcomes, quality of life, or cost effectiveness, they wrote. This recommendation applies for both tissue biomarkers and circulating tumor biomarkers.

The guidelines also recommend that carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 can be used as adjunctive assessments and can contribute to decisions regarding therapy. The data thus far, however, are insufficient to recommend their use alone for monitoring response to treatment. This recommendation, according to the researchers, is based on clinical experience and the informal consensus of the panel, since there are no studies that have been designed to evaluate the clinical utility of the markers.

It is also reasonable for clinicians to not use these markers as adjunctive assessments.

Outside of clinical trials, decisions for systemic therapy should be influenced by ER, PR, and HER2 status, as the clinical usefulness for other biomarkers has not yet been demonstrated. A number of other types of biomarkers are in active development, but there is insufficient evidence at this time showing that their use improves cancer outcomes, the panel said.

Biomarker distribution of ER, PR, and HER2 status may also differ across ethnic and racial backgrounds, and in addition to the biologic variability of these biomarkers, there is also evidence that disparities exist in the frequency of biomarker testing in certain populations.

The Food and Drug Administration has approved carfilzomib (Kyprolis) to be used in combination with lenalidomide (Revlimid) and dexamethasone for patients with relapsed multiple myeloma who have received one to three prior lines of therapy.

The expanded indication for carfilzomib was based on the results of the ASPIRE trial of 792 patients with relapsed or refractory multiple myeloma who were randomized to receive lenalidomide and dexamethasone with or without carfilzomib for 18 cycles. Progression-free survival was significantly longer among patients receiving the three-drug regimen that included carfilzomib (26.3 months), compared with those in the two-drug arm (17.6 months).

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The safety profile of carfilzomib used in combination was similar to that described on the current label. Side effects that occurred more frequently with the three-drug regimen included cardiovascular events, venous thromboembolic events, and thrombocytopenia.

Along with the approval, the labeling has been revised to include new warnings and precautions for venous thromboembolic events, cardiac toxicities, acute renal failure, pulmonary toxicities, and hypertension. Also, there are increased safety risks indicated for elderly patients.

The recommended dose-schedule for carfilzomib has also been revised for use as monotherapy or in combination with lenalidomide and dexamethasone.

Carfilzomib is manufactured by Onyx Pharmaceuticals under the trade name Kyprolis.

The Food and Drug Administration has approved carfilzomib (Kyprolis) to be used in combination with lenalidomide (Revlimid) and dexamethasone for patients with relapsed multiple myeloma who have received one to three prior lines of therapy.

The expanded indication for carfilzomib was based on the results of the ASPIRE trial of 792 patients with relapsed or refractory multiple myeloma who were randomized to receive lenalidomide and dexamethasone with or without carfilzomib for 18 cycles. Progression-free survival was significantly longer among patients receiving the three-drug regimen that included carfilzomib (26.3 months), compared with those in the two-drug arm (17.6 months).

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The safety profile of carfilzomib used in combination was similar to that described on the current label. Side effects that occurred more frequently with the three-drug regimen included cardiovascular events, venous thromboembolic events, and thrombocytopenia.

Along with the approval, the labeling has been revised to include new warnings and precautions for venous thromboembolic events, cardiac toxicities, acute renal failure, pulmonary toxicities, and hypertension. Also, there are increased safety risks indicated for elderly patients.

The recommended dose-schedule for carfilzomib has also been revised for use as monotherapy or in combination with lenalidomide and dexamethasone.

Carfilzomib is manufactured by Onyx Pharmaceuticals under the trade name Kyprolis.

The Food and Drug Administration has approved carfilzomib (Kyprolis) to be used in combination with lenalidomide (Revlimid) and dexamethasone for patients with relapsed multiple myeloma who have received one to three prior lines of therapy.

The expanded indication for carfilzomib was based on the results of the ASPIRE trial of 792 patients with relapsed or refractory multiple myeloma who were randomized to receive lenalidomide and dexamethasone with or without carfilzomib for 18 cycles. Progression-free survival was significantly longer among patients receiving the three-drug regimen that included carfilzomib (26.3 months), compared with those in the two-drug arm (17.6 months).

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

The safety profile of carfilzomib used in combination was similar to that described on the current label. Side effects that occurred more frequently with the three-drug regimen included cardiovascular events, venous thromboembolic events, and thrombocytopenia.

Along with the approval, the labeling has been revised to include new warnings and precautions for venous thromboembolic events, cardiac toxicities, acute renal failure, pulmonary toxicities, and hypertension. Also, there are increased safety risks indicated for elderly patients.

The recommended dose-schedule for carfilzomib has also been revised for use as monotherapy or in combination with lenalidomide and dexamethasone.

Carfilzomib is manufactured by Onyx Pharmaceuticals under the trade name Kyprolis.

Younger women who are diagnosed with low-grade serous ovarian carcinoma and those with persistent disease after the completion of their primary therapy have the worst outcomes, according to a study published online July 20 in Journal of Clinical Oncology.

Patients with low grade serous peritoneum cancer (LGSPC) also appeared to have a better prognosis than did those with low grade serous ovarian cancer (LGSOC).

From a cohort of 350 eligible patients identified from a database at a single center, women with LGSPC had significantly longer progression-free survival and overall survival compared with those with LGSOC (PFS: 36.2 v 25.4 months; P = .02; and OS: 129.0 vs. 95.2 months; P = .01, respectively).

Age also played a role in outcomes. Women diagnosed when they were older than 35 years had longer median progression-free survival compared with women diagnosed at age 35 years or younger (32.6 months vs 18.8 months; P less than .001).

In addition, patients with persistent disease at the end of their primary therapy had a 1.79 greater chance of progression or recurrence compared with those without it (P less than .001).

In the multivariable setting, only age, primary site, and disease status at end of primary therapy remained significant predictors of disease progression or recurrence.

“The principal findings of this study confirm the results of our original publication, indicating that relative to patients with high-grade ovarian or peritoneal cancers, women with low-grade serous carcinoma are younger on average and have prolonged OS,” wrote Dr. David M. Gershenson of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. “In addition, we found that three factors seemed to have a significant influence on patient outcomes: disease status at completion of primary treatment, age, and primary site of disease,” they wrote (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.0873]).

Younger women who are diagnosed with low-grade serous ovarian carcinoma and those with persistent disease after the completion of their primary therapy have the worst outcomes, according to a study published online July 20 in Journal of Clinical Oncology.

Patients with low grade serous peritoneum cancer (LGSPC) also appeared to have a better prognosis than did those with low grade serous ovarian cancer (LGSOC).

From a cohort of 350 eligible patients identified from a database at a single center, women with LGSPC had significantly longer progression-free survival and overall survival compared with those with LGSOC (PFS: 36.2 v 25.4 months; P = .02; and OS: 129.0 vs. 95.2 months; P = .01, respectively).

Age also played a role in outcomes. Women diagnosed when they were older than 35 years had longer median progression-free survival compared with women diagnosed at age 35 years or younger (32.6 months vs 18.8 months; P less than .001).

In addition, patients with persistent disease at the end of their primary therapy had a 1.79 greater chance of progression or recurrence compared with those without it (P less than .001).

In the multivariable setting, only age, primary site, and disease status at end of primary therapy remained significant predictors of disease progression or recurrence.

“The principal findings of this study confirm the results of our original publication, indicating that relative to patients with high-grade ovarian or peritoneal cancers, women with low-grade serous carcinoma are younger on average and have prolonged OS,” wrote Dr. David M. Gershenson of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. “In addition, we found that three factors seemed to have a significant influence on patient outcomes: disease status at completion of primary treatment, age, and primary site of disease,” they wrote (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.0873]).

Younger women who are diagnosed with low-grade serous ovarian carcinoma and those with persistent disease after the completion of their primary therapy have the worst outcomes, according to a study published online July 20 in Journal of Clinical Oncology.

Patients with low grade serous peritoneum cancer (LGSPC) also appeared to have a better prognosis than did those with low grade serous ovarian cancer (LGSOC).

From a cohort of 350 eligible patients identified from a database at a single center, women with LGSPC had significantly longer progression-free survival and overall survival compared with those with LGSOC (PFS: 36.2 v 25.4 months; P = .02; and OS: 129.0 vs. 95.2 months; P = .01, respectively).

Age also played a role in outcomes. Women diagnosed when they were older than 35 years had longer median progression-free survival compared with women diagnosed at age 35 years or younger (32.6 months vs 18.8 months; P less than .001).

In addition, patients with persistent disease at the end of their primary therapy had a 1.79 greater chance of progression or recurrence compared with those without it (P less than .001).

In the multivariable setting, only age, primary site, and disease status at end of primary therapy remained significant predictors of disease progression or recurrence.

“The principal findings of this study confirm the results of our original publication, indicating that relative to patients with high-grade ovarian or peritoneal cancers, women with low-grade serous carcinoma are younger on average and have prolonged OS,” wrote Dr. David M. Gershenson of the University of Texas MD Anderson Cancer Center, Houston, and colleagues. “In addition, we found that three factors seemed to have a significant influence on patient outcomes: disease status at completion of primary treatment, age, and primary site of disease,” they wrote (J. Clin. Oncol. 2015 July 20 [doi:10.1200/JCO.2015.61.0873]).

LYNNWOOD, WASH. — Use of exhaled nitric oxide as an adjunct for diagnosis and management of asthma is now available in some centers, but may be more widely available in the near future, Dr. Jason S. Debley said at a conference sponsored by the North Pacific Pediatric Society.

A special noninvasive analyzer is used to measure exhaled nitric oxide (eNO); however, a significant drawback is that the analyzers are very expensive. “What may break this field open is a portable device that is used in Europe,” one that the Food and Drug Administration is reviewing now, said Dr. Debley of the University of Washington, Seattle.

Asthma, the most common chronic disease of childhood, is an inflammatory condition. Nitric oxide is important in coordinating the immune response but in asthma patients, the concentration of nitric oxide in exhaled air is increased. Measurement of eNO concentration in the breath can be used to monitor asthma airway inflammation.

The combination of bronchial hyperactivity and inflammation leads to symptoms in patients with asthma. Because asthma is an inflammatory disease, national guidelines recommend that children with persistent asthma be treated with daily inhaled steroids. Treatment decisions usually are based on assessments of symptoms and traditional measures of lung function, which do not directly or objectively measure underlying eosinophilic airway inflammation, explained Dr. Debley.

The traditional approach to asthma diagnosis consists of evaluating symptoms, a physical examination that is often normal, and pulmonary function testing. “Spirometry is a useful test, but it can typically only be performed in children over age 6 years, and many children with mild to moderate asthma have normal spirometry readings at their baseline,” Dr. Debley said. “So it has significant limitations.”

Traditional methods of assessing airway inflammation, namely bronchoalveolar lavage, bronchial biopsy, or sputum analysis, are invasive, may require anesthesia, and/or are impossible to perform in children, Dr. Debley pointed out. In contrast, eNO is a noninvasive biomarker of lower airway eosinophilic airway inflammation.

Nitric oxide is a simple molecule, which was once thought of as a pollutant. “It is now known to be one of the most important molecules in human physiology,” Dr. Debley said.

Levels of eNO are higher in asthma patients, compared with nonasthmatic patients, and levels decrease after corticosteroid treatment in patients with asthma. The excess nitric oxide seen in asthma patients is primarily caused by an increase in the expression of the enzyme inducible nitric oxide synthase by airway epithelial cells.

In addition to helping diagnose asthma, eNO can be useful in predicting steroid responsiveness, said Dr. Debley. “It can also be used as a marker of compliance, to determine who is taking their medications.”

eNO does have its limitations, as eNO levels do not always correlate with National Institutes of Health classifications of asthma severity, and eNO is not always associated with measures of airflow obstruction. Therefore, eNO should not be used by itself to assess asthma severity, but rather as a complementary tool to spirometry.

Dr. Debley pointed out that eNO is used at his institution, and most children aged 6 years and older can perform the procedure. “Many 4- and 5-year-olds are also able to complete the test,” he said. “It is easier and more fun to perform than spirometry, and the kids don't seem to mind it.”

Another promising future tool is the measurement of biomarkers in exhaled breath condensate (EBC), which is collected by cooling or freezing exhaled breath. It is then analyzed for the presence of inflammatory mediators, cytokines, and other proteins, which have been detected in EBC.

EBC is another area of interest, although the field is still in its infancy, compared with eNO, Dr. Debley said. In patients with asthma, leukotriene and interleukin-4 levels in EBC are reported to be higher, compared with those in healthy individuals.

However, published literature has been inconsistent with regard to levels of leukotriene and other mediators in EBC between asthma and healthy patients, and in some cases, attempts to detect leukotrienes in EBC using commercially available assays have been unsuccessful.

LYNNWOOD, WASH. — Use of exhaled nitric oxide as an adjunct for diagnosis and management of asthma is now available in some centers, but may be more widely available in the near future, Dr. Jason S. Debley said at a conference sponsored by the North Pacific Pediatric Society.

A special noninvasive analyzer is used to measure exhaled nitric oxide (eNO); however, a significant drawback is that the analyzers are very expensive. “What may break this field open is a portable device that is used in Europe,” one that the Food and Drug Administration is reviewing now, said Dr. Debley of the University of Washington, Seattle.

Asthma, the most common chronic disease of childhood, is an inflammatory condition. Nitric oxide is important in coordinating the immune response but in asthma patients, the concentration of nitric oxide in exhaled air is increased. Measurement of eNO concentration in the breath can be used to monitor asthma airway inflammation.

The combination of bronchial hyperactivity and inflammation leads to symptoms in patients with asthma. Because asthma is an inflammatory disease, national guidelines recommend that children with persistent asthma be treated with daily inhaled steroids. Treatment decisions usually are based on assessments of symptoms and traditional measures of lung function, which do not directly or objectively measure underlying eosinophilic airway inflammation, explained Dr. Debley.

The traditional approach to asthma diagnosis consists of evaluating symptoms, a physical examination that is often normal, and pulmonary function testing. “Spirometry is a useful test, but it can typically only be performed in children over age 6 years, and many children with mild to moderate asthma have normal spirometry readings at their baseline,” Dr. Debley said. “So it has significant limitations.”

Traditional methods of assessing airway inflammation, namely bronchoalveolar lavage, bronchial biopsy, or sputum analysis, are invasive, may require anesthesia, and/or are impossible to perform in children, Dr. Debley pointed out. In contrast, eNO is a noninvasive biomarker of lower airway eosinophilic airway inflammation.

Nitric oxide is a simple molecule, which was once thought of as a pollutant. “It is now known to be one of the most important molecules in human physiology,” Dr. Debley said.

Levels of eNO are higher in asthma patients, compared with nonasthmatic patients, and levels decrease after corticosteroid treatment in patients with asthma. The excess nitric oxide seen in asthma patients is primarily caused by an increase in the expression of the enzyme inducible nitric oxide synthase by airway epithelial cells.

In addition to helping diagnose asthma, eNO can be useful in predicting steroid responsiveness, said Dr. Debley. “It can also be used as a marker of compliance, to determine who is taking their medications.”

eNO does have its limitations, as eNO levels do not always correlate with National Institutes of Health classifications of asthma severity, and eNO is not always associated with measures of airflow obstruction. Therefore, eNO should not be used by itself to assess asthma severity, but rather as a complementary tool to spirometry.

Dr. Debley pointed out that eNO is used at his institution, and most children aged 6 years and older can perform the procedure. “Many 4- and 5-year-olds are also able to complete the test,” he said. “It is easier and more fun to perform than spirometry, and the kids don't seem to mind it.”

Another promising future tool is the measurement of biomarkers in exhaled breath condensate (EBC), which is collected by cooling or freezing exhaled breath. It is then analyzed for the presence of inflammatory mediators, cytokines, and other proteins, which have been detected in EBC.

EBC is another area of interest, although the field is still in its infancy, compared with eNO, Dr. Debley said. In patients with asthma, leukotriene and interleukin-4 levels in EBC are reported to be higher, compared with those in healthy individuals.

However, published literature has been inconsistent with regard to levels of leukotriene and other mediators in EBC between asthma and healthy patients, and in some cases, attempts to detect leukotrienes in EBC using commercially available assays have been unsuccessful.

LYNNWOOD, WASH. — Use of exhaled nitric oxide as an adjunct for diagnosis and management of asthma is now available in some centers, but may be more widely available in the near future, Dr. Jason S. Debley said at a conference sponsored by the North Pacific Pediatric Society.

A special noninvasive analyzer is used to measure exhaled nitric oxide (eNO); however, a significant drawback is that the analyzers are very expensive. “What may break this field open is a portable device that is used in Europe,” one that the Food and Drug Administration is reviewing now, said Dr. Debley of the University of Washington, Seattle.

Asthma, the most common chronic disease of childhood, is an inflammatory condition. Nitric oxide is important in coordinating the immune response but in asthma patients, the concentration of nitric oxide in exhaled air is increased. Measurement of eNO concentration in the breath can be used to monitor asthma airway inflammation.

The combination of bronchial hyperactivity and inflammation leads to symptoms in patients with asthma. Because asthma is an inflammatory disease, national guidelines recommend that children with persistent asthma be treated with daily inhaled steroids. Treatment decisions usually are based on assessments of symptoms and traditional measures of lung function, which do not directly or objectively measure underlying eosinophilic airway inflammation, explained Dr. Debley.

The traditional approach to asthma diagnosis consists of evaluating symptoms, a physical examination that is often normal, and pulmonary function testing. “Spirometry is a useful test, but it can typically only be performed in children over age 6 years, and many children with mild to moderate asthma have normal spirometry readings at their baseline,” Dr. Debley said. “So it has significant limitations.”

Traditional methods of assessing airway inflammation, namely bronchoalveolar lavage, bronchial biopsy, or sputum analysis, are invasive, may require anesthesia, and/or are impossible to perform in children, Dr. Debley pointed out. In contrast, eNO is a noninvasive biomarker of lower airway eosinophilic airway inflammation.

Nitric oxide is a simple molecule, which was once thought of as a pollutant. “It is now known to be one of the most important molecules in human physiology,” Dr. Debley said.

Levels of eNO are higher in asthma patients, compared with nonasthmatic patients, and levels decrease after corticosteroid treatment in patients with asthma. The excess nitric oxide seen in asthma patients is primarily caused by an increase in the expression of the enzyme inducible nitric oxide synthase by airway epithelial cells.

In addition to helping diagnose asthma, eNO can be useful in predicting steroid responsiveness, said Dr. Debley. “It can also be used as a marker of compliance, to determine who is taking their medications.”

eNO does have its limitations, as eNO levels do not always correlate with National Institutes of Health classifications of asthma severity, and eNO is not always associated with measures of airflow obstruction. Therefore, eNO should not be used by itself to assess asthma severity, but rather as a complementary tool to spirometry.

Dr. Debley pointed out that eNO is used at his institution, and most children aged 6 years and older can perform the procedure. “Many 4- and 5-year-olds are also able to complete the test,” he said. “It is easier and more fun to perform than spirometry, and the kids don't seem to mind it.”

Another promising future tool is the measurement of biomarkers in exhaled breath condensate (EBC), which is collected by cooling or freezing exhaled breath. It is then analyzed for the presence of inflammatory mediators, cytokines, and other proteins, which have been detected in EBC.

EBC is another area of interest, although the field is still in its infancy, compared with eNO, Dr. Debley said. In patients with asthma, leukotriene and interleukin-4 levels in EBC are reported to be higher, compared with those in healthy individuals.

However, published literature has been inconsistent with regard to levels of leukotriene and other mediators in EBC between asthma and healthy patients, and in some cases, attempts to detect leukotrienes in EBC using commercially available assays have been unsuccessful.

LYNNWOOD, WASH. — An influenza pandemic may seem abstract right now, but it will happen, Dr. Kathryn Koelemay, M.P.H., said at a conference sponsored by the North Pacific Pediatric Society.

“The time that we spend preparing for it will be time well spent,” she said.

Pediatricians can start now to ready their office and staff for such an event.

There have been three influenza pandemics during the past century, with the most notable being the Spanish flu, which circled the globe in 1918–1919. Smaller pandemics occurred in 1957–1958 and 1968–1969.

The most pressing concern currently is the outbreak of avian flu, caused by the highly pathogenic H5N1 strain, which first appeared in birds in 1997. Influenza viruses are common in birds, explained Dr. Koelemay, a medical epidemiologist at the Department of Public Health of Seattle and King County, Wash. “They affect birds all of the time, but they are generally of low pathogenicity.”

Since 1997, the highly pathogenic strain of influenza type A H5N1 has infected birds in more than 50 countries, and to date, 12 nations have reported human cases.

The mortality is very high in human avian flu infections, Dr. Koelemay explained, but it is not easily spread among human populations.

All cases thus far have involved close contact with infected birds or family members, and no sustained human-to-human transmission has been reported. In fact, it remains very difficult for a person to be infected with avian flu, which continues to be largely a disease of birds.

Many experts warn that we are unprepared for a global influenza pandemic, which may be overdue, and the avian H5N1 is the most likely candidate. Even though human transmission remains limited, the potential for viral mutation persists. Evidence from 1918 suggests that the Spanish flu evolved from avian origin, so it is not inconceivable that it could happen again.

“One of the major differences between now and 1918 is the greater degree of human migration. We know that the flu will move around the world much more quickly,” said Dr. Koelemay.

Government agencies are making plans for this, but we also need to rely as much as possible on our own resources, she added.

Community strategies will involve measures that include isolation and treatment of known cases, and voluntary home quarantine of family members of patients with influenza. Other pandemic mitigation interventions call for the closure of child care programs and schools, and the use of social distancing measures to reduce contact between adults in the community and workplace.

Pediatricians need to prepare themselves and their office staff for a possible pandemic. A major problem during any type of emergency is the difficulty in getting health care workers to report to work. Dr. Koelemay explained that the most frequently cited reason for the unwillingness of employees to report to work during a disaster was fear and concern for their own safety and that of their family.

“You need to ask yourself what you can do now to make sure that you can report to work during a health emergency,” said Dr. Koelemay.

Pediatricians and their employees need to develop a personal family emergency and disaster plan.

Additionally, expectations of health care workers also must be clarified in advance of a pandemic. Job expectations during a pandemic need to be specified, along with alternative work assignments for employees with medical conditions that place them at an increased risk, and policies for absenteeism, leave, and compensation.

The severe acute respiratory syndrome (SARS) outbreak taught us valuable lessons, which may help protect health care workers in the event of an influenza pandemic. SARS was transmitted to health care workers because of a lack of infection-control precautions and training, an inconsistent use of personal protective equipment, and the use of aerosol-generating procedures without requiring fit-tested N-95 equivalent respirators.

“You have to train everyone in your facility—even down to the person who sits at the front desk,” Dr. Koelemay said.

Effective education and training of all workers, providing appropriate protective equipment with sufficient training on how to use it properly, and establishing clear policies and protocols will help to alleviate fear among employees.

Pediatrics practices will encounter some specific challenges in the event of a pandemic, Dr. Koelemay pointed out.

“In pediatrics, beds tend to be more centralized than the patients are,” she said.

Designated pediatric beds may not be available in all area hospitals, and there may be only minimal planning in the outpatient community.

Caring for children during a pandemic will require trained personnel, equipment, and supplies suitable for a pediatric population, she said.

LYNNWOOD, WASH. — An influenza pandemic may seem abstract right now, but it will happen, Dr. Kathryn Koelemay, M.P.H., said at a conference sponsored by the North Pacific Pediatric Society.

“The time that we spend preparing for it will be time well spent,” she said.

Pediatricians can start now to ready their office and staff for such an event.

There have been three influenza pandemics during the past century, with the most notable being the Spanish flu, which circled the globe in 1918–1919. Smaller pandemics occurred in 1957–1958 and 1968–1969.

The most pressing concern currently is the outbreak of avian flu, caused by the highly pathogenic H5N1 strain, which first appeared in birds in 1997. Influenza viruses are common in birds, explained Dr. Koelemay, a medical epidemiologist at the Department of Public Health of Seattle and King County, Wash. “They affect birds all of the time, but they are generally of low pathogenicity.”

Since 1997, the highly pathogenic strain of influenza type A H5N1 has infected birds in more than 50 countries, and to date, 12 nations have reported human cases.

The mortality is very high in human avian flu infections, Dr. Koelemay explained, but it is not easily spread among human populations.

All cases thus far have involved close contact with infected birds or family members, and no sustained human-to-human transmission has been reported. In fact, it remains very difficult for a person to be infected with avian flu, which continues to be largely a disease of birds.

Many experts warn that we are unprepared for a global influenza pandemic, which may be overdue, and the avian H5N1 is the most likely candidate. Even though human transmission remains limited, the potential for viral mutation persists. Evidence from 1918 suggests that the Spanish flu evolved from avian origin, so it is not inconceivable that it could happen again.

“One of the major differences between now and 1918 is the greater degree of human migration. We know that the flu will move around the world much more quickly,” said Dr. Koelemay.

Government agencies are making plans for this, but we also need to rely as much as possible on our own resources, she added.

Community strategies will involve measures that include isolation and treatment of known cases, and voluntary home quarantine of family members of patients with influenza. Other pandemic mitigation interventions call for the closure of child care programs and schools, and the use of social distancing measures to reduce contact between adults in the community and workplace.

Pediatricians need to prepare themselves and their office staff for a possible pandemic. A major problem during any type of emergency is the difficulty in getting health care workers to report to work. Dr. Koelemay explained that the most frequently cited reason for the unwillingness of employees to report to work during a disaster was fear and concern for their own safety and that of their family.

“You need to ask yourself what you can do now to make sure that you can report to work during a health emergency,” said Dr. Koelemay.

Pediatricians and their employees need to develop a personal family emergency and disaster plan.

Additionally, expectations of health care workers also must be clarified in advance of a pandemic. Job expectations during a pandemic need to be specified, along with alternative work assignments for employees with medical conditions that place them at an increased risk, and policies for absenteeism, leave, and compensation.

The severe acute respiratory syndrome (SARS) outbreak taught us valuable lessons, which may help protect health care workers in the event of an influenza pandemic. SARS was transmitted to health care workers because of a lack of infection-control precautions and training, an inconsistent use of personal protective equipment, and the use of aerosol-generating procedures without requiring fit-tested N-95 equivalent respirators.

“You have to train everyone in your facility—even down to the person who sits at the front desk,” Dr. Koelemay said.

Effective education and training of all workers, providing appropriate protective equipment with sufficient training on how to use it properly, and establishing clear policies and protocols will help to alleviate fear among employees.

Pediatrics practices will encounter some specific challenges in the event of a pandemic, Dr. Koelemay pointed out.

“In pediatrics, beds tend to be more centralized than the patients are,” she said.

Designated pediatric beds may not be available in all area hospitals, and there may be only minimal planning in the outpatient community.

Caring for children during a pandemic will require trained personnel, equipment, and supplies suitable for a pediatric population, she said.

LYNNWOOD, WASH. — An influenza pandemic may seem abstract right now, but it will happen, Dr. Kathryn Koelemay, M.P.H., said at a conference sponsored by the North Pacific Pediatric Society.

“The time that we spend preparing for it will be time well spent,” she said.

Pediatricians can start now to ready their office and staff for such an event.

There have been three influenza pandemics during the past century, with the most notable being the Spanish flu, which circled the globe in 1918–1919. Smaller pandemics occurred in 1957–1958 and 1968–1969.

The most pressing concern currently is the outbreak of avian flu, caused by the highly pathogenic H5N1 strain, which first appeared in birds in 1997. Influenza viruses are common in birds, explained Dr. Koelemay, a medical epidemiologist at the Department of Public Health of Seattle and King County, Wash. “They affect birds all of the time, but they are generally of low pathogenicity.”

Since 1997, the highly pathogenic strain of influenza type A H5N1 has infected birds in more than 50 countries, and to date, 12 nations have reported human cases.

The mortality is very high in human avian flu infections, Dr. Koelemay explained, but it is not easily spread among human populations.

All cases thus far have involved close contact with infected birds or family members, and no sustained human-to-human transmission has been reported. In fact, it remains very difficult for a person to be infected with avian flu, which continues to be largely a disease of birds.

Many experts warn that we are unprepared for a global influenza pandemic, which may be overdue, and the avian H5N1 is the most likely candidate. Even though human transmission remains limited, the potential for viral mutation persists. Evidence from 1918 suggests that the Spanish flu evolved from avian origin, so it is not inconceivable that it could happen again.

“One of the major differences between now and 1918 is the greater degree of human migration. We know that the flu will move around the world much more quickly,” said Dr. Koelemay.

Government agencies are making plans for this, but we also need to rely as much as possible on our own resources, she added.

Community strategies will involve measures that include isolation and treatment of known cases, and voluntary home quarantine of family members of patients with influenza. Other pandemic mitigation interventions call for the closure of child care programs and schools, and the use of social distancing measures to reduce contact between adults in the community and workplace.

Pediatricians need to prepare themselves and their office staff for a possible pandemic. A major problem during any type of emergency is the difficulty in getting health care workers to report to work. Dr. Koelemay explained that the most frequently cited reason for the unwillingness of employees to report to work during a disaster was fear and concern for their own safety and that of their family.

“You need to ask yourself what you can do now to make sure that you can report to work during a health emergency,” said Dr. Koelemay.

Pediatricians and their employees need to develop a personal family emergency and disaster plan.

Additionally, expectations of health care workers also must be clarified in advance of a pandemic. Job expectations during a pandemic need to be specified, along with alternative work assignments for employees with medical conditions that place them at an increased risk, and policies for absenteeism, leave, and compensation.

The severe acute respiratory syndrome (SARS) outbreak taught us valuable lessons, which may help protect health care workers in the event of an influenza pandemic. SARS was transmitted to health care workers because of a lack of infection-control precautions and training, an inconsistent use of personal protective equipment, and the use of aerosol-generating procedures without requiring fit-tested N-95 equivalent respirators.

“You have to train everyone in your facility—even down to the person who sits at the front desk,” Dr. Koelemay said.

Effective education and training of all workers, providing appropriate protective equipment with sufficient training on how to use it properly, and establishing clear policies and protocols will help to alleviate fear among employees.

Pediatrics practices will encounter some specific challenges in the event of a pandemic, Dr. Koelemay pointed out.

“In pediatrics, beds tend to be more centralized than the patients are,” she said.

Designated pediatric beds may not be available in all area hospitals, and there may be only minimal planning in the outpatient community.

Caring for children during a pandemic will require trained personnel, equipment, and supplies suitable for a pediatric population, she said.

SAN ANTONIO – Lack of nearby pain practices helps explain why only about 5% of U.S. adults with chronic pain ever see a pain specialist, Brenda Breuer, Ph.D., said at the annual meeting of the American Pain Society.

The finding comes from a survey of 748 pain specialists who responded to a survey that was sent to about 2,500 pain specialists certified by the American Board of Medical Specialties or the American Board of Pain Medicine.

“We felt that if we identified any deficiencies, that would be a first step towards improvement,” explained Dr. Breuer of the department of pain medicine and palliative care at Beth Israel Medical Center, New York.

The specialties, age, and geographic location of the physicians who responded to the survey were similar to those of the nonresponders. Most (74%) had primary training in anesthesiology, whereas others were trained in physiatry (15%), neurology (5%), psychiatry (3%), and other areas (11%).

Analysis of census data showed that individuals residing near pain practices were similar to the general U.S. population. Pain practices were underrepresented in rural areas, and people living near pain specialists tended to have higher incomes and higher education levels that the general population.

Academic physicians, who accounted for about one-third of the respondents, were more likely than others to have had their primary training in neurology, and were more likely to have completed a pain fellowship. They were also more likely to be associated with a facility involved in research, to hospitalize patients for aggressive treatment of severe pain, and to have interdisciplinary practices.

Respondents in practices that focus on a specific modality (29%) were more likely than others to have had their primary training in anesthesiology, and were significantly less likely to have interdisciplinary practices, to prescribe and maintain patients on controlled substances, to follow patients longitudinally, and to hospitalize for aggressive treatment of severe pain. They were also more likely than others to treat pain in only one part of the body, such as headaches.

Conversely, physicians in multimodality, comprehensive practices were more likely to use opioids and to collaborate with specialists. They were also likely to have an integrated practice, which included not only physicians of different specialties but also a psychologist, a physician assistant, and a social worker.

Board certification does not imply a uniform approach to chronic pain treatment. Nationally, there are only six board-certified pain physicians per 100,000 adult chronic pain patients, but it is as yet unclear whether there is a shortage, she said.

“Future surveys of pain patients are needed to complement physicians' surveys to assess the actual efficacy of pain management,” Dr. Breuer said.

SAN ANTONIO – Lack of nearby pain practices helps explain why only about 5% of U.S. adults with chronic pain ever see a pain specialist, Brenda Breuer, Ph.D., said at the annual meeting of the American Pain Society.

The finding comes from a survey of 748 pain specialists who responded to a survey that was sent to about 2,500 pain specialists certified by the American Board of Medical Specialties or the American Board of Pain Medicine.

“We felt that if we identified any deficiencies, that would be a first step towards improvement,” explained Dr. Breuer of the department of pain medicine and palliative care at Beth Israel Medical Center, New York.

The specialties, age, and geographic location of the physicians who responded to the survey were similar to those of the nonresponders. Most (74%) had primary training in anesthesiology, whereas others were trained in physiatry (15%), neurology (5%), psychiatry (3%), and other areas (11%).

Analysis of census data showed that individuals residing near pain practices were similar to the general U.S. population. Pain practices were underrepresented in rural areas, and people living near pain specialists tended to have higher incomes and higher education levels that the general population.

Academic physicians, who accounted for about one-third of the respondents, were more likely than others to have had their primary training in neurology, and were more likely to have completed a pain fellowship. They were also more likely to be associated with a facility involved in research, to hospitalize patients for aggressive treatment of severe pain, and to have interdisciplinary practices.

Respondents in practices that focus on a specific modality (29%) were more likely than others to have had their primary training in anesthesiology, and were significantly less likely to have interdisciplinary practices, to prescribe and maintain patients on controlled substances, to follow patients longitudinally, and to hospitalize for aggressive treatment of severe pain. They were also more likely than others to treat pain in only one part of the body, such as headaches.

Conversely, physicians in multimodality, comprehensive practices were more likely to use opioids and to collaborate with specialists. They were also likely to have an integrated practice, which included not only physicians of different specialties but also a psychologist, a physician assistant, and a social worker.

Board certification does not imply a uniform approach to chronic pain treatment. Nationally, there are only six board-certified pain physicians per 100,000 adult chronic pain patients, but it is as yet unclear whether there is a shortage, she said.

“Future surveys of pain patients are needed to complement physicians' surveys to assess the actual efficacy of pain management,” Dr. Breuer said.

SAN ANTONIO – Lack of nearby pain practices helps explain why only about 5% of U.S. adults with chronic pain ever see a pain specialist, Brenda Breuer, Ph.D., said at the annual meeting of the American Pain Society.

The finding comes from a survey of 748 pain specialists who responded to a survey that was sent to about 2,500 pain specialists certified by the American Board of Medical Specialties or the American Board of Pain Medicine.

“We felt that if we identified any deficiencies, that would be a first step towards improvement,” explained Dr. Breuer of the department of pain medicine and palliative care at Beth Israel Medical Center, New York.

The specialties, age, and geographic location of the physicians who responded to the survey were similar to those of the nonresponders. Most (74%) had primary training in anesthesiology, whereas others were trained in physiatry (15%), neurology (5%), psychiatry (3%), and other areas (11%).

Analysis of census data showed that individuals residing near pain practices were similar to the general U.S. population. Pain practices were underrepresented in rural areas, and people living near pain specialists tended to have higher incomes and higher education levels that the general population.

Academic physicians, who accounted for about one-third of the respondents, were more likely than others to have had their primary training in neurology, and were more likely to have completed a pain fellowship. They were also more likely to be associated with a facility involved in research, to hospitalize patients for aggressive treatment of severe pain, and to have interdisciplinary practices.

Respondents in practices that focus on a specific modality (29%) were more likely than others to have had their primary training in anesthesiology, and were significantly less likely to have interdisciplinary practices, to prescribe and maintain patients on controlled substances, to follow patients longitudinally, and to hospitalize for aggressive treatment of severe pain. They were also more likely than others to treat pain in only one part of the body, such as headaches.

Conversely, physicians in multimodality, comprehensive practices were more likely to use opioids and to collaborate with specialists. They were also likely to have an integrated practice, which included not only physicians of different specialties but also a psychologist, a physician assistant, and a social worker.

Board certification does not imply a uniform approach to chronic pain treatment. Nationally, there are only six board-certified pain physicians per 100,000 adult chronic pain patients, but it is as yet unclear whether there is a shortage, she said.

“Future surveys of pain patients are needed to complement physicians' surveys to assess the actual efficacy of pain management,” Dr. Breuer said.