Preparing for radiation

Photo by Rhoda Baer

Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.

However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.

Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.

The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.

However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.

To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.

The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.

“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.

Results in males

The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).

In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.

They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).

They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).

And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).

The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).

The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.

“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”

Results in females

The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.

The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.

However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).

Preparing for radiation

Photo by Rhoda Baer

Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.

However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.

Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.

The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.

However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.

To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.

The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.

“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.

Results in males

The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).

In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.

They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).

They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).

And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).

The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).

The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.

“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”

Results in females

The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.

The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.

However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).

Preparing for radiation

Photo by Rhoda Baer

Radiologists who graduated from medical school after 1940 do not have an increased risk of dying from radiation-related causes such as cancers, according to a study published in Radiology.

However, the study suggested that male radiologists who graduated before 1940 had a higher risk of death from certain cancers, including acute myeloid leukemia and non-Hodgkin lymphoma.

Researchers said these findings point to the success of efforts to reduce occupational radiation doses over the past several decades.

The team noted that female radiologists did not have an increased risk of all-cause mortality or cancer-related mortality, regardless of when they graduated from medical school.

However, the small number of women in this study prevented the researchers from studying the subjects’ mortality rates in detail. And very few female radiologists worked during the early period of the study, when radiation exposures were likely highest.

To conduct this study, the researchers analyzed records from the American Medical Association Physician Masterfile, a database established in 1906 that has grown to include current and historical data for more than 1.4 million physicians, residents, and medical students in the US.

The team compared cancer incidence and mortality rates between 43,763 radiologists and 64,990 psychiatrists who graduated from medical school between 1916 and 2006. Psychiatrists were chosen as a comparison group because they are unlikely to have had occupational radiation exposure.

“Our most important finding is that radiologists have lower death rates from all causes of death combined, compared to psychiatrists, and had similar risks of cancer deaths overall,” said study author Martha Linet, MD, of the National Cancer Institute in Bethesda, Maryland.

Results in males

The researchers found that, among male subjects who graduated after 1940, the risk of all-cause mortality was lower for the radiologists than the psychiatrists (relative risk [RR]=0.94; 95% CI: 0.90, 0.97), and the risk of death from cancer was similar (RR=1.00; 95% CI: 0.93, 1.07).

In contrast, male radiologists who graduated before 1940 had higher mortality rates from certain cancers.

They had a higher risk of skin cancer mortality (RR=6.38; 95% CI: 1.75, 23.20) that was driven by an excess of melanoma (RR=8.75; 95% CI: 1.89, 40.53).

They had an increased risk of death from all myeloid leukemias (RR=1.43; 95% CI: 1.00, 2.05) that was driven by acute myeloid leukemia and/or myelodysplastic syndromes (RR=4.68; 95% CI: 0.91, 24.18).

And they had an increased risk of death from lymphomas (RR=2.24; 95% CI: 1.31, 3.86) that was driven by non-Hodgkin lymphoma (RR=2.69; 95% CI: 1.33, 5.45).

The researchers also found an increased risk of cerebrovascular deaths in the male radiologists who graduated before 1940 (RR=1.49; 95% CI: 1.11, 2.01).

The team said the reduced health risks for more recent radiology graduates are likely due to developments and improvements in radiation protection and monitoring, along with improvements in equipment safety.

“Most of the findings of increased risk were in the earlier radiologists,” Dr Linet noted. “We do feel there is evidence that decreases in dose in the United States and other countries seem to have paid off, reducing risks in recent graduates.”

Results in females

The researchers said there were no clear increases in mortality in the female radiologists compared with the female psychiatrists.

The risk of all-cause mortality was lower in the radiologists, as was the risk of death from circulatory diseases, but the risk of cancer-related mortality was similar between the radiologists and the psychiatrists.

However, the researchers said the relatively small number of female deaths in this study prevented detailed investigation. Only 2% of female radiologists (208/8851) and 3% of female psychiatrists (524/17,493) died, compared to 12% of male radiologists (4260/43,763) and 16% of male psychiatrists (7815/47,443).

Chemotherapy drugs

Photo by Bill Branson

Results of a phase 3 study suggest the antipsychotic agent olanzapine can also be used to reduce nausea and vomiting caused by chemotherapy.

In this study, cancer patients receiving highly emetogenic chemotherapy also received combination anti-emetic therapy including olanzapine or placebo.

Those patients who received olanzapine were significantly less likely to experience nausea and vomiting in the 120 hours after starting chemotherapy.

These results were published in NEJM.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, of Sanford Cancer Center in Sioux Falls, South Dakota.

“The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

Dr Powell and his colleagues evaluated cancer patients who had received no previous chemotherapy but were receiving cisplatin or cyclophosphamide and doxorubicin during the study period.

To prevent nausea and vomiting, all of the patients received a 5-HT3–receptor antagonist, dexamethasone, and an NK1-receptor antagonist. Roughly half also received olanzapine, and the other half received placebo.

Overall, 380 patients were evaluable—192 assigned to olanzapine and 188 to placebo.

In the first 24 hours after starting chemotherapy, the proportion of patients who did not have chemotherapy-induced nausea was significantly greater in the olanzapine arm than the placebo arm—74% and 45%, respectively (P=0.002).

The same was true at 25 hours to 120 hours after the start of chemotherapy—42% and 25%, respectively (P=0.002)—and for the overall 120-hour period—37% and 22%, respectively (P=0.002).

The complete response rate—defined as no vomiting and no rescue therapy—was significantly higher in the olanzapine arm than the placebo arm in the first 24 hours—86% and 65% (P<0.001)—at 25 hours to 120 hours—67% and 52%, respectively (P=0.007)—and overall—64% and 41%, respectively (P<0.001).

There were two grade 3 adverse events and three grade 4 adverse events in the olanzapine arm, but none of these were attributed to olanzapine.

Patients in the olanzapine arm had significantly increased sedation on day 2 compared with baseline, but this resolved on days 3, 4, and 5, although the patients were still receiving olanzapine on days 3 and 4.

Chemotherapy drugs

Photo by Bill Branson

Results of a phase 3 study suggest the antipsychotic agent olanzapine can also be used to reduce nausea and vomiting caused by chemotherapy.

In this study, cancer patients receiving highly emetogenic chemotherapy also received combination anti-emetic therapy including olanzapine or placebo.

Those patients who received olanzapine were significantly less likely to experience nausea and vomiting in the 120 hours after starting chemotherapy.

These results were published in NEJM.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, of Sanford Cancer Center in Sioux Falls, South Dakota.

“The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

Dr Powell and his colleagues evaluated cancer patients who had received no previous chemotherapy but were receiving cisplatin or cyclophosphamide and doxorubicin during the study period.

To prevent nausea and vomiting, all of the patients received a 5-HT3–receptor antagonist, dexamethasone, and an NK1-receptor antagonist. Roughly half also received olanzapine, and the other half received placebo.

Overall, 380 patients were evaluable—192 assigned to olanzapine and 188 to placebo.

In the first 24 hours after starting chemotherapy, the proportion of patients who did not have chemotherapy-induced nausea was significantly greater in the olanzapine arm than the placebo arm—74% and 45%, respectively (P=0.002).

The same was true at 25 hours to 120 hours after the start of chemotherapy—42% and 25%, respectively (P=0.002)—and for the overall 120-hour period—37% and 22%, respectively (P=0.002).

The complete response rate—defined as no vomiting and no rescue therapy—was significantly higher in the olanzapine arm than the placebo arm in the first 24 hours—86% and 65% (P<0.001)—at 25 hours to 120 hours—67% and 52%, respectively (P=0.007)—and overall—64% and 41%, respectively (P<0.001).

There were two grade 3 adverse events and three grade 4 adverse events in the olanzapine arm, but none of these were attributed to olanzapine.

Patients in the olanzapine arm had significantly increased sedation on day 2 compared with baseline, but this resolved on days 3, 4, and 5, although the patients were still receiving olanzapine on days 3 and 4.

Chemotherapy drugs

Photo by Bill Branson

Results of a phase 3 study suggest the antipsychotic agent olanzapine can also be used to reduce nausea and vomiting caused by chemotherapy.

In this study, cancer patients receiving highly emetogenic chemotherapy also received combination anti-emetic therapy including olanzapine or placebo.

Those patients who received olanzapine were significantly less likely to experience nausea and vomiting in the 120 hours after starting chemotherapy.

These results were published in NEJM.

“We’ve long known the nausea and vomiting that come along with chemotherapy are a major problem and affect the quality of life of our patients,” said study author Steven Powell, MD, of Sanford Cancer Center in Sioux Falls, South Dakota.

“The findings of this study, fortunately, provide physicians with a tool to better address the needs of those they are treating for cancer.”

Dr Powell and his colleagues evaluated cancer patients who had received no previous chemotherapy but were receiving cisplatin or cyclophosphamide and doxorubicin during the study period.

To prevent nausea and vomiting, all of the patients received a 5-HT3–receptor antagonist, dexamethasone, and an NK1-receptor antagonist. Roughly half also received olanzapine, and the other half received placebo.

Overall, 380 patients were evaluable—192 assigned to olanzapine and 188 to placebo.

In the first 24 hours after starting chemotherapy, the proportion of patients who did not have chemotherapy-induced nausea was significantly greater in the olanzapine arm than the placebo arm—74% and 45%, respectively (P=0.002).

The same was true at 25 hours to 120 hours after the start of chemotherapy—42% and 25%, respectively (P=0.002)—and for the overall 120-hour period—37% and 22%, respectively (P=0.002).

The complete response rate—defined as no vomiting and no rescue therapy—was significantly higher in the olanzapine arm than the placebo arm in the first 24 hours—86% and 65% (P<0.001)—at 25 hours to 120 hours—67% and 52%, respectively (P=0.007)—and overall—64% and 41%, respectively (P<0.001).

There were two grade 3 adverse events and three grade 4 adverse events in the olanzapine arm, but none of these were attributed to olanzapine.

Patients in the olanzapine arm had significantly increased sedation on day 2 compared with baseline, but this resolved on days 3, 4, and 5, although the patients were still receiving olanzapine on days 3 and 4.

CHICAGO – The survival impact of resecting the primary tumor in women with de novo stage IV breast cancer depends on receipt of and response to prior systemic therapy, suggested a pair of studies reported at the annual meeting of the American Society of Clinical Oncology.

A randomized trial conducted in Turkey found that, relative to peers who received initial systemic therapy, women who underwent initial resection of the primary tumor had a one-third lower risk of death at 5 years. But a prospective registry study conducted in the United States found that elective resection after a response to first-line therapy did not significantly improve overall survival, with patients living roughly 6 years regardless of whether they had the surgery or not.

Findings in context

“I think these studies have just confirmed what we know, and that is that tumor biology is critical,” said invited discussant Elizabeth A. Mittendorf, MD, PhD, of University of Texas MD Anderson Cancer Center, Houston. “Patients who do not respond to systemic therapy will do poorly, so I don’t think it’s unwise to consider a biologic ‘stress test’ with initiation of first-line therapy, knowing that patients who do not respond will not benefit from surgery.”

Those with hormone receptor–positive or HER2-positive disease are most likely to benefit from targeted therapy and may see even higher response rates as novel targeted agents are introduced. “But despite the increase in response to therapy, we really have no data at this time to suggest any benefit from surgery,” she added. “There may be some utility in continuing to enroll these patients in a clinical trial. I would suggest that it would need to be a subtype-specific trial and would question whether we have the appetite to conduct such a study.”

More information on managing de novo stage IV breast cancer is expected from ongoing trials such as the Eastern Cooperative Oncology Group’s 2108 trial, which is randomizing patients having a response or stable disease with first-line therapy to either early local therapy or delayed local therapy only at the time of progression, according to Dr. Mittendorf.

Poor accrual necessitated redesign of the trial. “As part of that redesign, there was a decrease in the target enrollment, which causes me concern that the trial will not be powered to inform its primary endpoint of overall survival,” she commented. However, “it’s interesting to note that in early 2014, shortly after the report of the trials from India and Turkey at the San Antonio Breast Cancer Symposium, there was a significant increase in enrollment, suggesting that this is a clinically important question.”

Turkish study: MF07-01

Susan London/Frontline Medical News

The first study – trial MF07-01 of the Turkish Federation of Breast Diseases Societies – was presented by Atilla Soran, MD, of Magee-Womens Hospital of University of Pittsburgh Medical Center.

He and his colleagues enrolled in the trial women with de novo stage IV breast cancer whose primary tumor was amenable to complete surgical resection and who were healthy enough to be treated.

The women were randomized evenly either to initial systemic therapy followed by local therapy only if local progression occurred, or to initial local therapy, consisting of surgery with or without radiation therapy of the breast and axilla, followed by systemic therapy.

Among the 274 evaluable women having a median follow-up of about 40 months, the 3-year rate of overall survival did not differ significantly between the two groups, Dr. Soran reported.

However, the 5-year rate of overall survival was 41.6% in the initial surgery group and 24.4% in the initial systemic therapy group, a difference translating to a significant reduction in the risk of death (hazard ratio, 0.66; P = .005). Median survival was 46 months and 37 months, respectively.

The benefit was similar in women whose tumors had hormone receptors, whose tumors were negative for HER2, and who were younger than age 55. There was no significant benefit of up-front surgery for women with bone-only metastases, “but we believe that when we follow these patients longer, the difference is going to be statistically significant,” he said.

On the other hand, there was a trend among women who had multiple pulmonary and/or liver metastases whereby they were more likely to die if they initially had surgery instead of systemic therapy.

Locoregional progression/relapse occurred in 1% of the initial surgery group but 11% of the initial systemic therapy group. Among women who did not have locoregional progression/relapse, surgery still had a survival benefit (HR, 0.61; P = .001).

“We know that with systemic therapy, immunotherapy, radiation therapy, and imaging as developments, patients are living longer when you compare to a decade ago or 20 years ago,” said Dr. Soran. “But we also believe that there is a role for surgery of the primary tumor in those patients.”

“Performance status, age, and comorbidities must be taken into account, and the burden of metastatic disease needs to be considered,” he maintained. “The benefit of surgery at presentation is dependent on the completeness of resection, and axillary surgery and locoregional radiation therapy should be considered regardless of the metastasis.”

U.S. study: TBCRC 013

Susan London/Frontline Medical News

The second study – the Translational Breast Cancer Research Consortium’s study 013 – was presented by Tari A. King, MD, chief of breast surgery at the Dana-Farber Cancer Institute, associate division chief for breast surgery at Brigham and Women’s Hospital, and associate professor of surgery at Harvard Medical School, all in Boston.

The investigators analyzed data from the study’s cohort A, consisting of 112 patients with de novo stage IV breast cancer who had an intact primary tumor. All patients were given first-line systemic therapy; those who had a response were additionally offered elective resection of their primary tumor.

The median duration of follow-up was 54 months. Overall, 85% of the women had a response to their first-line therapy, Dr. King reported.

Some 43% of responders opted to undergo elective surgery to resect their primary tumor, defined as surgery performed in the absence of local symptoms or the need for local control, with specific type and extent left up to the treating physician.

In a multivariate analysis among responders surviving at least 6 months, median survival was 71 months with elective surgery and 65 months without it, a nonsignificant difference.

Findings were similar among subsets of women having estrogen receptor–positive tumors or HER2-positive tumors, and various combinations of these features.

In recursive partitioning analysis, response to first-line therapy, HER2 status, and age were the major determinants of survival.

“Importantly, although we were not able to demonstrate a survival benefit with the use of surgery, surgery also did not impact progression-free survival,” noted Dr. King.

Ultimately, 4% of responders who did not have elective surgery and 18% of nonresponders went on to have palliative resection of their primary.

“As this was a registry study, patients selected for surgery were more likely to have single-organ metastatic disease and to have received first-line chemotherapy, yet despite this selection bias, surgery did not impact survival in any tumor subtype,” Dr. King summarized. “Among patients who responded to therapy, HER2 status and patient age remained strong prognostic factors. Further investigation is needed to determine if subsets of patients will ultimately benefit from surgery.”

“In the absence of additional prospective data, our findings do not support surgery for the primary tumor outside of a clinical trial,” she concluded.

CHICAGO – The survival impact of resecting the primary tumor in women with de novo stage IV breast cancer depends on receipt of and response to prior systemic therapy, suggested a pair of studies reported at the annual meeting of the American Society of Clinical Oncology.

A randomized trial conducted in Turkey found that, relative to peers who received initial systemic therapy, women who underwent initial resection of the primary tumor had a one-third lower risk of death at 5 years. But a prospective registry study conducted in the United States found that elective resection after a response to first-line therapy did not significantly improve overall survival, with patients living roughly 6 years regardless of whether they had the surgery or not.

Findings in context

“I think these studies have just confirmed what we know, and that is that tumor biology is critical,” said invited discussant Elizabeth A. Mittendorf, MD, PhD, of University of Texas MD Anderson Cancer Center, Houston. “Patients who do not respond to systemic therapy will do poorly, so I don’t think it’s unwise to consider a biologic ‘stress test’ with initiation of first-line therapy, knowing that patients who do not respond will not benefit from surgery.”

Those with hormone receptor–positive or HER2-positive disease are most likely to benefit from targeted therapy and may see even higher response rates as novel targeted agents are introduced. “But despite the increase in response to therapy, we really have no data at this time to suggest any benefit from surgery,” she added. “There may be some utility in continuing to enroll these patients in a clinical trial. I would suggest that it would need to be a subtype-specific trial and would question whether we have the appetite to conduct such a study.”

More information on managing de novo stage IV breast cancer is expected from ongoing trials such as the Eastern Cooperative Oncology Group’s 2108 trial, which is randomizing patients having a response or stable disease with first-line therapy to either early local therapy or delayed local therapy only at the time of progression, according to Dr. Mittendorf.

Poor accrual necessitated redesign of the trial. “As part of that redesign, there was a decrease in the target enrollment, which causes me concern that the trial will not be powered to inform its primary endpoint of overall survival,” she commented. However, “it’s interesting to note that in early 2014, shortly after the report of the trials from India and Turkey at the San Antonio Breast Cancer Symposium, there was a significant increase in enrollment, suggesting that this is a clinically important question.”

Turkish study: MF07-01

Susan London/Frontline Medical News

The first study – trial MF07-01 of the Turkish Federation of Breast Diseases Societies – was presented by Atilla Soran, MD, of Magee-Womens Hospital of University of Pittsburgh Medical Center.

He and his colleagues enrolled in the trial women with de novo stage IV breast cancer whose primary tumor was amenable to complete surgical resection and who were healthy enough to be treated.

The women were randomized evenly either to initial systemic therapy followed by local therapy only if local progression occurred, or to initial local therapy, consisting of surgery with or without radiation therapy of the breast and axilla, followed by systemic therapy.

Among the 274 evaluable women having a median follow-up of about 40 months, the 3-year rate of overall survival did not differ significantly between the two groups, Dr. Soran reported.

However, the 5-year rate of overall survival was 41.6% in the initial surgery group and 24.4% in the initial systemic therapy group, a difference translating to a significant reduction in the risk of death (hazard ratio, 0.66; P = .005). Median survival was 46 months and 37 months, respectively.

The benefit was similar in women whose tumors had hormone receptors, whose tumors were negative for HER2, and who were younger than age 55. There was no significant benefit of up-front surgery for women with bone-only metastases, “but we believe that when we follow these patients longer, the difference is going to be statistically significant,” he said.

On the other hand, there was a trend among women who had multiple pulmonary and/or liver metastases whereby they were more likely to die if they initially had surgery instead of systemic therapy.

Locoregional progression/relapse occurred in 1% of the initial surgery group but 11% of the initial systemic therapy group. Among women who did not have locoregional progression/relapse, surgery still had a survival benefit (HR, 0.61; P = .001).

“We know that with systemic therapy, immunotherapy, radiation therapy, and imaging as developments, patients are living longer when you compare to a decade ago or 20 years ago,” said Dr. Soran. “But we also believe that there is a role for surgery of the primary tumor in those patients.”

“Performance status, age, and comorbidities must be taken into account, and the burden of metastatic disease needs to be considered,” he maintained. “The benefit of surgery at presentation is dependent on the completeness of resection, and axillary surgery and locoregional radiation therapy should be considered regardless of the metastasis.”

U.S. study: TBCRC 013

Susan London/Frontline Medical News

The second study – the Translational Breast Cancer Research Consortium’s study 013 – was presented by Tari A. King, MD, chief of breast surgery at the Dana-Farber Cancer Institute, associate division chief for breast surgery at Brigham and Women’s Hospital, and associate professor of surgery at Harvard Medical School, all in Boston.

The investigators analyzed data from the study’s cohort A, consisting of 112 patients with de novo stage IV breast cancer who had an intact primary tumor. All patients were given first-line systemic therapy; those who had a response were additionally offered elective resection of their primary tumor.

The median duration of follow-up was 54 months. Overall, 85% of the women had a response to their first-line therapy, Dr. King reported.

Some 43% of responders opted to undergo elective surgery to resect their primary tumor, defined as surgery performed in the absence of local symptoms or the need for local control, with specific type and extent left up to the treating physician.

In a multivariate analysis among responders surviving at least 6 months, median survival was 71 months with elective surgery and 65 months without it, a nonsignificant difference.

Findings were similar among subsets of women having estrogen receptor–positive tumors or HER2-positive tumors, and various combinations of these features.

In recursive partitioning analysis, response to first-line therapy, HER2 status, and age were the major determinants of survival.

“Importantly, although we were not able to demonstrate a survival benefit with the use of surgery, surgery also did not impact progression-free survival,” noted Dr. King.

Ultimately, 4% of responders who did not have elective surgery and 18% of nonresponders went on to have palliative resection of their primary.

“As this was a registry study, patients selected for surgery were more likely to have single-organ metastatic disease and to have received first-line chemotherapy, yet despite this selection bias, surgery did not impact survival in any tumor subtype,” Dr. King summarized. “Among patients who responded to therapy, HER2 status and patient age remained strong prognostic factors. Further investigation is needed to determine if subsets of patients will ultimately benefit from surgery.”

“In the absence of additional prospective data, our findings do not support surgery for the primary tumor outside of a clinical trial,” she concluded.

CHICAGO – The survival impact of resecting the primary tumor in women with de novo stage IV breast cancer depends on receipt of and response to prior systemic therapy, suggested a pair of studies reported at the annual meeting of the American Society of Clinical Oncology.

A randomized trial conducted in Turkey found that, relative to peers who received initial systemic therapy, women who underwent initial resection of the primary tumor had a one-third lower risk of death at 5 years. But a prospective registry study conducted in the United States found that elective resection after a response to first-line therapy did not significantly improve overall survival, with patients living roughly 6 years regardless of whether they had the surgery or not.

Findings in context

“I think these studies have just confirmed what we know, and that is that tumor biology is critical,” said invited discussant Elizabeth A. Mittendorf, MD, PhD, of University of Texas MD Anderson Cancer Center, Houston. “Patients who do not respond to systemic therapy will do poorly, so I don’t think it’s unwise to consider a biologic ‘stress test’ with initiation of first-line therapy, knowing that patients who do not respond will not benefit from surgery.”

Those with hormone receptor–positive or HER2-positive disease are most likely to benefit from targeted therapy and may see even higher response rates as novel targeted agents are introduced. “But despite the increase in response to therapy, we really have no data at this time to suggest any benefit from surgery,” she added. “There may be some utility in continuing to enroll these patients in a clinical trial. I would suggest that it would need to be a subtype-specific trial and would question whether we have the appetite to conduct such a study.”

More information on managing de novo stage IV breast cancer is expected from ongoing trials such as the Eastern Cooperative Oncology Group’s 2108 trial, which is randomizing patients having a response or stable disease with first-line therapy to either early local therapy or delayed local therapy only at the time of progression, according to Dr. Mittendorf.

Poor accrual necessitated redesign of the trial. “As part of that redesign, there was a decrease in the target enrollment, which causes me concern that the trial will not be powered to inform its primary endpoint of overall survival,” she commented. However, “it’s interesting to note that in early 2014, shortly after the report of the trials from India and Turkey at the San Antonio Breast Cancer Symposium, there was a significant increase in enrollment, suggesting that this is a clinically important question.”

Turkish study: MF07-01

Susan London/Frontline Medical News

The first study – trial MF07-01 of the Turkish Federation of Breast Diseases Societies – was presented by Atilla Soran, MD, of Magee-Womens Hospital of University of Pittsburgh Medical Center.

He and his colleagues enrolled in the trial women with de novo stage IV breast cancer whose primary tumor was amenable to complete surgical resection and who were healthy enough to be treated.

The women were randomized evenly either to initial systemic therapy followed by local therapy only if local progression occurred, or to initial local therapy, consisting of surgery with or without radiation therapy of the breast and axilla, followed by systemic therapy.

Among the 274 evaluable women having a median follow-up of about 40 months, the 3-year rate of overall survival did not differ significantly between the two groups, Dr. Soran reported.

However, the 5-year rate of overall survival was 41.6% in the initial surgery group and 24.4% in the initial systemic therapy group, a difference translating to a significant reduction in the risk of death (hazard ratio, 0.66; P = .005). Median survival was 46 months and 37 months, respectively.

The benefit was similar in women whose tumors had hormone receptors, whose tumors were negative for HER2, and who were younger than age 55. There was no significant benefit of up-front surgery for women with bone-only metastases, “but we believe that when we follow these patients longer, the difference is going to be statistically significant,” he said.

On the other hand, there was a trend among women who had multiple pulmonary and/or liver metastases whereby they were more likely to die if they initially had surgery instead of systemic therapy.

Locoregional progression/relapse occurred in 1% of the initial surgery group but 11% of the initial systemic therapy group. Among women who did not have locoregional progression/relapse, surgery still had a survival benefit (HR, 0.61; P = .001).

“We know that with systemic therapy, immunotherapy, radiation therapy, and imaging as developments, patients are living longer when you compare to a decade ago or 20 years ago,” said Dr. Soran. “But we also believe that there is a role for surgery of the primary tumor in those patients.”

“Performance status, age, and comorbidities must be taken into account, and the burden of metastatic disease needs to be considered,” he maintained. “The benefit of surgery at presentation is dependent on the completeness of resection, and axillary surgery and locoregional radiation therapy should be considered regardless of the metastasis.”

U.S. study: TBCRC 013

Susan London/Frontline Medical News

The second study – the Translational Breast Cancer Research Consortium’s study 013 – was presented by Tari A. King, MD, chief of breast surgery at the Dana-Farber Cancer Institute, associate division chief for breast surgery at Brigham and Women’s Hospital, and associate professor of surgery at Harvard Medical School, all in Boston.

The investigators analyzed data from the study’s cohort A, consisting of 112 patients with de novo stage IV breast cancer who had an intact primary tumor. All patients were given first-line systemic therapy; those who had a response were additionally offered elective resection of their primary tumor.

The median duration of follow-up was 54 months. Overall, 85% of the women had a response to their first-line therapy, Dr. King reported.

Some 43% of responders opted to undergo elective surgery to resect their primary tumor, defined as surgery performed in the absence of local symptoms or the need for local control, with specific type and extent left up to the treating physician.

In a multivariate analysis among responders surviving at least 6 months, median survival was 71 months with elective surgery and 65 months without it, a nonsignificant difference.

Findings were similar among subsets of women having estrogen receptor–positive tumors or HER2-positive tumors, and various combinations of these features.

In recursive partitioning analysis, response to first-line therapy, HER2 status, and age were the major determinants of survival.

“Importantly, although we were not able to demonstrate a survival benefit with the use of surgery, surgery also did not impact progression-free survival,” noted Dr. King.

Ultimately, 4% of responders who did not have elective surgery and 18% of nonresponders went on to have palliative resection of their primary.

“As this was a registry study, patients selected for surgery were more likely to have single-organ metastatic disease and to have received first-line chemotherapy, yet despite this selection bias, surgery did not impact survival in any tumor subtype,” Dr. King summarized. “Among patients who responded to therapy, HER2 status and patient age remained strong prognostic factors. Further investigation is needed to determine if subsets of patients will ultimately benefit from surgery.”

“In the absence of additional prospective data, our findings do not support surgery for the primary tumor outside of a clinical trial,” she concluded.

New aspergillosis guidelines from the Infectious Diseases Society of America recommend serum and bronchoalveolar lavage galactomannan as a marker for the diagnosis of invasive Aspergillus in adult and pediatric patients who have hematologic malignancies or have undergone hematopoietic stem cell transplants.

Serial monitoring of serum galactomannan (GM) is also useful to monitor disease progression, therapeutic response, and prognosis in hematologic malignancy and hematopoietic stem cell transplant (HSCT) patients who have elevated baseline GM (Clin Infect Dis. 2016 Jun 29. doi: 10.1093/cid/ciw326).

Serum beta-D-glucan assays also are recommended for diagnosing invasive Aspergillus (IA) in high-risk hematologic malignancy and allogeneic HSCT patients, although these tests are not very specific for the infection.

The advice illustrates the Society’s emphasis on early diagnosis in its new guidelines, which supplant the group’s 2008 guidance. There are almost 100 recommendations covering – in depth – the management of invasive, allergic, and chronic Aspergillus infections in all their manifestations. It’s a step-by-step, how-to manual for handling the problem.

“Aspergillosis mortality rates have decreased significantly in recent years, but there is still significant mortality from the infection, and we have a ways to go. We felt that early diagnosis was key, which is why it’s such an important part of these guidelines,” said lead author Thomas Patterson, MD, chief of the Division of Infectious Diseases at the University of Texas Health Science Center, San Antonio. He highlighted the most important developments in a recent interview.

“We know a lot more since 2008 about the benefits of using biomarkers like GM in bronchoalveolar lavage samples, which could be highly useful for diagnosis. However, biomarkers have not been as well validated for biologic response and are not recommended” in most cases for monitoring how well patients are doing. Also, “biomarkers are not as useful in solid organ transplants; we discuss that” in the guidelines, Dr. Patterson said.

The society came out against routine polymerase chain reaction (PCR) testing of blood samples for diagnosis. Although there has been a lot of work on the technique, the evidence isn’t strong enough yet to establish overall clinical benefit, but there is emerging evidence for the diagnostic use of PCR in conjunction with radiologic findings.

For treatment, voriconazole remains the go-to drug, but the guidelines make room for more recently approved therapies. “We now have isavuconazole, which may be better tolerated,” but it’s recommended only as an alternative to voriconazole because evidence comes mostly from a single clinical trial, he said.

Posaconazole extended-release tablets are strongly recommended as prophylaxis based on high-quality evidence from studies in neutropenic patients. Posaconazole extended-release tablets result in significantly higher antifungal blood levels than those seen with voriconazole, and “it certainly has been useful in some patients”; however, posaconazole is not approved for primary therapy in the United States, Dr. Patterson said.

A large clinical trial that tested voriconazole plus an echinocandin against voriconazole alone found that in patients diagnosed using serum galactomannan – especially those with hematologic malignancies – outcomes were better with the combination. “The panel felt combinations could be considered in some patients” but didn’t recommend them for routine use because [again,] there’s not strong evidence,” he said.

For now, it seems that higher-risk patients with hematologic malignancies and those with more widespread disease might be the ones who benefit most from combination therapy.

“We also discussed allergic and saprophytic diseases. We know that some patients with allergic bronchopulmonary aspergillosis will respond to antifungal therapy, and perhaps reduce their need for steroids, so that’s now part of the suggestions, as well,” he said.

The IDSA funded the work. Dr. Patterson receives research funding from Astellas, Merck, and Revolution Medicines, and has been an adviser to numerous drug companies.

[email protected]

New aspergillosis guidelines from the Infectious Diseases Society of America recommend serum and bronchoalveolar lavage galactomannan as a marker for the diagnosis of invasive Aspergillus in adult and pediatric patients who have hematologic malignancies or have undergone hematopoietic stem cell transplants.

Serial monitoring of serum galactomannan (GM) is also useful to monitor disease progression, therapeutic response, and prognosis in hematologic malignancy and hematopoietic stem cell transplant (HSCT) patients who have elevated baseline GM (Clin Infect Dis. 2016 Jun 29. doi: 10.1093/cid/ciw326).

Serum beta-D-glucan assays also are recommended for diagnosing invasive Aspergillus (IA) in high-risk hematologic malignancy and allogeneic HSCT patients, although these tests are not very specific for the infection.

The advice illustrates the Society’s emphasis on early diagnosis in its new guidelines, which supplant the group’s 2008 guidance. There are almost 100 recommendations covering – in depth – the management of invasive, allergic, and chronic Aspergillus infections in all their manifestations. It’s a step-by-step, how-to manual for handling the problem.

“Aspergillosis mortality rates have decreased significantly in recent years, but there is still significant mortality from the infection, and we have a ways to go. We felt that early diagnosis was key, which is why it’s such an important part of these guidelines,” said lead author Thomas Patterson, MD, chief of the Division of Infectious Diseases at the University of Texas Health Science Center, San Antonio. He highlighted the most important developments in a recent interview.

“We know a lot more since 2008 about the benefits of using biomarkers like GM in bronchoalveolar lavage samples, which could be highly useful for diagnosis. However, biomarkers have not been as well validated for biologic response and are not recommended” in most cases for monitoring how well patients are doing. Also, “biomarkers are not as useful in solid organ transplants; we discuss that” in the guidelines, Dr. Patterson said.

The society came out against routine polymerase chain reaction (PCR) testing of blood samples for diagnosis. Although there has been a lot of work on the technique, the evidence isn’t strong enough yet to establish overall clinical benefit, but there is emerging evidence for the diagnostic use of PCR in conjunction with radiologic findings.

For treatment, voriconazole remains the go-to drug, but the guidelines make room for more recently approved therapies. “We now have isavuconazole, which may be better tolerated,” but it’s recommended only as an alternative to voriconazole because evidence comes mostly from a single clinical trial, he said.

Posaconazole extended-release tablets are strongly recommended as prophylaxis based on high-quality evidence from studies in neutropenic patients. Posaconazole extended-release tablets result in significantly higher antifungal blood levels than those seen with voriconazole, and “it certainly has been useful in some patients”; however, posaconazole is not approved for primary therapy in the United States, Dr. Patterson said.

A large clinical trial that tested voriconazole plus an echinocandin against voriconazole alone found that in patients diagnosed using serum galactomannan – especially those with hematologic malignancies – outcomes were better with the combination. “The panel felt combinations could be considered in some patients” but didn’t recommend them for routine use because [again,] there’s not strong evidence,” he said.

For now, it seems that higher-risk patients with hematologic malignancies and those with more widespread disease might be the ones who benefit most from combination therapy.

“We also discussed allergic and saprophytic diseases. We know that some patients with allergic bronchopulmonary aspergillosis will respond to antifungal therapy, and perhaps reduce their need for steroids, so that’s now part of the suggestions, as well,” he said.

The IDSA funded the work. Dr. Patterson receives research funding from Astellas, Merck, and Revolution Medicines, and has been an adviser to numerous drug companies.

[email protected]

New aspergillosis guidelines from the Infectious Diseases Society of America recommend serum and bronchoalveolar lavage galactomannan as a marker for the diagnosis of invasive Aspergillus in adult and pediatric patients who have hematologic malignancies or have undergone hematopoietic stem cell transplants.

Serial monitoring of serum galactomannan (GM) is also useful to monitor disease progression, therapeutic response, and prognosis in hematologic malignancy and hematopoietic stem cell transplant (HSCT) patients who have elevated baseline GM (Clin Infect Dis. 2016 Jun 29. doi: 10.1093/cid/ciw326).

Serum beta-D-glucan assays also are recommended for diagnosing invasive Aspergillus (IA) in high-risk hematologic malignancy and allogeneic HSCT patients, although these tests are not very specific for the infection.

The advice illustrates the Society’s emphasis on early diagnosis in its new guidelines, which supplant the group’s 2008 guidance. There are almost 100 recommendations covering – in depth – the management of invasive, allergic, and chronic Aspergillus infections in all their manifestations. It’s a step-by-step, how-to manual for handling the problem.

“Aspergillosis mortality rates have decreased significantly in recent years, but there is still significant mortality from the infection, and we have a ways to go. We felt that early diagnosis was key, which is why it’s such an important part of these guidelines,” said lead author Thomas Patterson, MD, chief of the Division of Infectious Diseases at the University of Texas Health Science Center, San Antonio. He highlighted the most important developments in a recent interview.

“We know a lot more since 2008 about the benefits of using biomarkers like GM in bronchoalveolar lavage samples, which could be highly useful for diagnosis. However, biomarkers have not been as well validated for biologic response and are not recommended” in most cases for monitoring how well patients are doing. Also, “biomarkers are not as useful in solid organ transplants; we discuss that” in the guidelines, Dr. Patterson said.

The society came out against routine polymerase chain reaction (PCR) testing of blood samples for diagnosis. Although there has been a lot of work on the technique, the evidence isn’t strong enough yet to establish overall clinical benefit, but there is emerging evidence for the diagnostic use of PCR in conjunction with radiologic findings.

For treatment, voriconazole remains the go-to drug, but the guidelines make room for more recently approved therapies. “We now have isavuconazole, which may be better tolerated,” but it’s recommended only as an alternative to voriconazole because evidence comes mostly from a single clinical trial, he said.

Posaconazole extended-release tablets are strongly recommended as prophylaxis based on high-quality evidence from studies in neutropenic patients. Posaconazole extended-release tablets result in significantly higher antifungal blood levels than those seen with voriconazole, and “it certainly has been useful in some patients”; however, posaconazole is not approved for primary therapy in the United States, Dr. Patterson said.

A large clinical trial that tested voriconazole plus an echinocandin against voriconazole alone found that in patients diagnosed using serum galactomannan – especially those with hematologic malignancies – outcomes were better with the combination. “The panel felt combinations could be considered in some patients” but didn’t recommend them for routine use because [again,] there’s not strong evidence,” he said.

For now, it seems that higher-risk patients with hematologic malignancies and those with more widespread disease might be the ones who benefit most from combination therapy.

“We also discussed allergic and saprophytic diseases. We know that some patients with allergic bronchopulmonary aspergillosis will respond to antifungal therapy, and perhaps reduce their need for steroids, so that’s now part of the suggestions, as well,” he said.

The IDSA funded the work. Dr. Patterson receives research funding from Astellas, Merck, and Revolution Medicines, and has been an adviser to numerous drug companies.

[email protected]

The 2014-2015 HIV infection outbreak in Indiana was associated with the injection-drug use of extended-release oxymorphone, according to a study published in the New England Journal of Medicine.

The study examined 181 HIV-1 infections diagnosed in patients in Scott County, Ind., from Nov. 18, 2014, to Nov. 1, 2015. Of these outbreak-related cases, a total of 159 patients (87.8%) reported injecting the extended-release formulation of the prescription opioid oxymorphone in the previous 12 months. In addition, 173 of the 181 patients reported other injection-drug use, including 47 (27.2%) who reported occasionally injecting heroin, 40 (23.1%) who reported injecting methamphetamine, 15 (8.7%) who reported injecting cocaine, and 2 (1.2%) who reported injecting oxycodone.

©Thinkstock.com

Researchers noted that the first three HIV cases in the patient network were detected during routine HIV screening, while eight more cases were diagnosed in syringe-sharing partners of these case patients. All 11 of these HIV-infected persons reported having injected oxymorphone, and a subsequent public health investigation that included contact tracing and phylogenetic analyses of HIV and hepatitis C virus (HCV) sequences revealed the extent of the outbreak. Ultimately, 167 case patients (92.3%) were coinfected with HCV before and during the outbreak.

“Although the proactive deployment of interventions for HIV prevention among persons who inject drugs is challenging in rural areas that have a low incidence of HIV but are at risk for an outbreak, the implementation of HIV testing and treatment, syringe-service programs, and medication-assisted treatment are necessary to help prevent a similar outbreak in the future,” the researchers concluded.

Read the full study here (doi:10.1056/NEJMoa1515195).

[email protected]

The 2014-2015 HIV infection outbreak in Indiana was associated with the injection-drug use of extended-release oxymorphone, according to a study published in the New England Journal of Medicine.

The study examined 181 HIV-1 infections diagnosed in patients in Scott County, Ind., from Nov. 18, 2014, to Nov. 1, 2015. Of these outbreak-related cases, a total of 159 patients (87.8%) reported injecting the extended-release formulation of the prescription opioid oxymorphone in the previous 12 months. In addition, 173 of the 181 patients reported other injection-drug use, including 47 (27.2%) who reported occasionally injecting heroin, 40 (23.1%) who reported injecting methamphetamine, 15 (8.7%) who reported injecting cocaine, and 2 (1.2%) who reported injecting oxycodone.

©Thinkstock.com

Researchers noted that the first three HIV cases in the patient network were detected during routine HIV screening, while eight more cases were diagnosed in syringe-sharing partners of these case patients. All 11 of these HIV-infected persons reported having injected oxymorphone, and a subsequent public health investigation that included contact tracing and phylogenetic analyses of HIV and hepatitis C virus (HCV) sequences revealed the extent of the outbreak. Ultimately, 167 case patients (92.3%) were coinfected with HCV before and during the outbreak.

“Although the proactive deployment of interventions for HIV prevention among persons who inject drugs is challenging in rural areas that have a low incidence of HIV but are at risk for an outbreak, the implementation of HIV testing and treatment, syringe-service programs, and medication-assisted treatment are necessary to help prevent a similar outbreak in the future,” the researchers concluded.

Read the full study here (doi:10.1056/NEJMoa1515195).

[email protected]

The 2014-2015 HIV infection outbreak in Indiana was associated with the injection-drug use of extended-release oxymorphone, according to a study published in the New England Journal of Medicine.

The study examined 181 HIV-1 infections diagnosed in patients in Scott County, Ind., from Nov. 18, 2014, to Nov. 1, 2015. Of these outbreak-related cases, a total of 159 patients (87.8%) reported injecting the extended-release formulation of the prescription opioid oxymorphone in the previous 12 months. In addition, 173 of the 181 patients reported other injection-drug use, including 47 (27.2%) who reported occasionally injecting heroin, 40 (23.1%) who reported injecting methamphetamine, 15 (8.7%) who reported injecting cocaine, and 2 (1.2%) who reported injecting oxycodone.

©Thinkstock.com

Researchers noted that the first three HIV cases in the patient network were detected during routine HIV screening, while eight more cases were diagnosed in syringe-sharing partners of these case patients. All 11 of these HIV-infected persons reported having injected oxymorphone, and a subsequent public health investigation that included contact tracing and phylogenetic analyses of HIV and hepatitis C virus (HCV) sequences revealed the extent of the outbreak. Ultimately, 167 case patients (92.3%) were coinfected with HCV before and during the outbreak.

“Although the proactive deployment of interventions for HIV prevention among persons who inject drugs is challenging in rural areas that have a low incidence of HIV but are at risk for an outbreak, the implementation of HIV testing and treatment, syringe-service programs, and medication-assisted treatment are necessary to help prevent a similar outbreak in the future,” the researchers concluded.

Read the full study here (doi:10.1056/NEJMoa1515195).

[email protected]

In February of 2016, the World Health Organization declared Zika a Public Health Emergency of International Concern and the Centers for Disease and Prevention elevated its Zika Emergency Operation Center activation to Level 1, its highest level. The Zika epidemic is unique in many ways, particularly in that women and reproductive health care are at the center of the epidemic.

Most people who are infected with Zika are asymptomatic; those who do have symptoms generally have a mild, self-limited infection. However, a pregnant woman can pass the infection to her fetus, which can lead to severe outcomes. As ob.gyns., we are called upon to guide pregnant women who have been exposed or infected regarding testing, diagnosis, options counseling, surveillance, and management. Additionally, we can help pregnant women prevent Zika infection. Discuss avoiding travel for her and her partner(s) to areas with Zika. Encourage strategies for mosquito bite prevention if traveling to endemic areas and at home. Recommend abstaining from sex or using a condom for those who have partners who have recently traveled to areas with Zika transmission.

With that said, most of our patients are not pregnant. Many are capable of pregnancy and potentially at risk for unintended pregnancy since almost half of pregnancies in the United States are unintended (N Engl J Med. 2016 Mar 3;374[9]:843-52). Contraception for women who are not desiring pregnancy may help prevent unintended pregnancy, but also may help prevent the serious effects that can be seen with mother-to-fetus transmission of Zika. We can play a critical role in this important prevention message for nonpregnant women.

We do not know how long the Zika virus will continue to spread nor do we know whether we will have local transmission in the continental U.S. But we do know that travel is common and sexual transmission is possible. As such, all women need to be educated about the Zika virus. All women should be aware of the risks it poses for their reproductive health and be given an opportunity to discuss what that might mean to each of them. Whether a woman is planning a pregnancy, trying to avoid one, or is unsure of what she wants, having a conversation with her ob.gyn. may help her feel informed and supported in making the best decision for her right now. This may be particularly true of her plans for pregnancy timing and the use of contraception and condoms.

Beyond travel screening and mosquito bite prevention strategies, there are several key messages that we are uniquely poised to relay about Zika prevention. First, women who have been exposed to Zika should delay trying to conceive for 8 weeks. The recommendation for male partners to delay conception ranges from 8 weeks to 6 months depending upon local transmission and presence of symptoms. For those who are not trying to become pregnant or who want to delay pregnancy because of Zika concerns or exposures, we should offer the full range of contraceptive options and work with each patient to optimize her contraceptive selection, based on her individual preferences, goals, and needs. Finally, women should be counseled to avoid transmission from sex by choosing to not have sex or by using a condom with each act of sex with a partner who may have been exposed to Zika.

Our understanding of Zika infection is rapidly evolving. It will be particularly important for us to stay current on this issue. Providers can access up-to-date information about Zika, provider updates, patient information, posters and other information about the emergency response from the CDC’s website at www.cdc.gov/zika/index.html.

There are several tools available for guidance in these conversations. On July 1, 2016, the Office of Population Affairs released a toolkit for Providing Family Planning Care for Non-Pregnant Women and Men of Reproductive Age in the Context of Zika. It is available online at: www.hhs.gov/opa/news#toolkit.

The CDC also offers comprehensive guidance on providing contraception. Providers can access the Medical Eligibility Criteria for Contraceptive Use, the Selected Practice Recommendations for Contraceptive Use, and Providing Quality Family Planning Services, all of which are available on the CDC website.

Dr. Kottke is an associate professor in the department of gynecology and obstetrics at Emory University in Atlanta, Georgia. She is the director of the Jane Fonda Center at Emory, which is involved in research and program development focused on adolescent sexual and reproductive health. She also serves as the medical consultant for the state of Georgia’s Family Planning Program. Dr. Kottke reported that she is a Nexplanon (Merck) trainer, is a consultant to CSL Behring, and serves on the advisory board for Evofem.

In February of 2016, the World Health Organization declared Zika a Public Health Emergency of International Concern and the Centers for Disease and Prevention elevated its Zika Emergency Operation Center activation to Level 1, its highest level. The Zika epidemic is unique in many ways, particularly in that women and reproductive health care are at the center of the epidemic.

Most people who are infected with Zika are asymptomatic; those who do have symptoms generally have a mild, self-limited infection. However, a pregnant woman can pass the infection to her fetus, which can lead to severe outcomes. As ob.gyns., we are called upon to guide pregnant women who have been exposed or infected regarding testing, diagnosis, options counseling, surveillance, and management. Additionally, we can help pregnant women prevent Zika infection. Discuss avoiding travel for her and her partner(s) to areas with Zika. Encourage strategies for mosquito bite prevention if traveling to endemic areas and at home. Recommend abstaining from sex or using a condom for those who have partners who have recently traveled to areas with Zika transmission.

With that said, most of our patients are not pregnant. Many are capable of pregnancy and potentially at risk for unintended pregnancy since almost half of pregnancies in the United States are unintended (N Engl J Med. 2016 Mar 3;374[9]:843-52). Contraception for women who are not desiring pregnancy may help prevent unintended pregnancy, but also may help prevent the serious effects that can be seen with mother-to-fetus transmission of Zika. We can play a critical role in this important prevention message for nonpregnant women.

We do not know how long the Zika virus will continue to spread nor do we know whether we will have local transmission in the continental U.S. But we do know that travel is common and sexual transmission is possible. As such, all women need to be educated about the Zika virus. All women should be aware of the risks it poses for their reproductive health and be given an opportunity to discuss what that might mean to each of them. Whether a woman is planning a pregnancy, trying to avoid one, or is unsure of what she wants, having a conversation with her ob.gyn. may help her feel informed and supported in making the best decision for her right now. This may be particularly true of her plans for pregnancy timing and the use of contraception and condoms.

Beyond travel screening and mosquito bite prevention strategies, there are several key messages that we are uniquely poised to relay about Zika prevention. First, women who have been exposed to Zika should delay trying to conceive for 8 weeks. The recommendation for male partners to delay conception ranges from 8 weeks to 6 months depending upon local transmission and presence of symptoms. For those who are not trying to become pregnant or who want to delay pregnancy because of Zika concerns or exposures, we should offer the full range of contraceptive options and work with each patient to optimize her contraceptive selection, based on her individual preferences, goals, and needs. Finally, women should be counseled to avoid transmission from sex by choosing to not have sex or by using a condom with each act of sex with a partner who may have been exposed to Zika.

Our understanding of Zika infection is rapidly evolving. It will be particularly important for us to stay current on this issue. Providers can access up-to-date information about Zika, provider updates, patient information, posters and other information about the emergency response from the CDC’s website at www.cdc.gov/zika/index.html.

There are several tools available for guidance in these conversations. On July 1, 2016, the Office of Population Affairs released a toolkit for Providing Family Planning Care for Non-Pregnant Women and Men of Reproductive Age in the Context of Zika. It is available online at: www.hhs.gov/opa/news#toolkit.

The CDC also offers comprehensive guidance on providing contraception. Providers can access the Medical Eligibility Criteria for Contraceptive Use, the Selected Practice Recommendations for Contraceptive Use, and Providing Quality Family Planning Services, all of which are available on the CDC website.

Dr. Kottke is an associate professor in the department of gynecology and obstetrics at Emory University in Atlanta, Georgia. She is the director of the Jane Fonda Center at Emory, which is involved in research and program development focused on adolescent sexual and reproductive health. She also serves as the medical consultant for the state of Georgia’s Family Planning Program. Dr. Kottke reported that she is a Nexplanon (Merck) trainer, is a consultant to CSL Behring, and serves on the advisory board for Evofem.

In February of 2016, the World Health Organization declared Zika a Public Health Emergency of International Concern and the Centers for Disease and Prevention elevated its Zika Emergency Operation Center activation to Level 1, its highest level. The Zika epidemic is unique in many ways, particularly in that women and reproductive health care are at the center of the epidemic.

Most people who are infected with Zika are asymptomatic; those who do have symptoms generally have a mild, self-limited infection. However, a pregnant woman can pass the infection to her fetus, which can lead to severe outcomes. As ob.gyns., we are called upon to guide pregnant women who have been exposed or infected regarding testing, diagnosis, options counseling, surveillance, and management. Additionally, we can help pregnant women prevent Zika infection. Discuss avoiding travel for her and her partner(s) to areas with Zika. Encourage strategies for mosquito bite prevention if traveling to endemic areas and at home. Recommend abstaining from sex or using a condom for those who have partners who have recently traveled to areas with Zika transmission.

With that said, most of our patients are not pregnant. Many are capable of pregnancy and potentially at risk for unintended pregnancy since almost half of pregnancies in the United States are unintended (N Engl J Med. 2016 Mar 3;374[9]:843-52). Contraception for women who are not desiring pregnancy may help prevent unintended pregnancy, but also may help prevent the serious effects that can be seen with mother-to-fetus transmission of Zika. We can play a critical role in this important prevention message for nonpregnant women.

We do not know how long the Zika virus will continue to spread nor do we know whether we will have local transmission in the continental U.S. But we do know that travel is common and sexual transmission is possible. As such, all women need to be educated about the Zika virus. All women should be aware of the risks it poses for their reproductive health and be given an opportunity to discuss what that might mean to each of them. Whether a woman is planning a pregnancy, trying to avoid one, or is unsure of what she wants, having a conversation with her ob.gyn. may help her feel informed and supported in making the best decision for her right now. This may be particularly true of her plans for pregnancy timing and the use of contraception and condoms.

Beyond travel screening and mosquito bite prevention strategies, there are several key messages that we are uniquely poised to relay about Zika prevention. First, women who have been exposed to Zika should delay trying to conceive for 8 weeks. The recommendation for male partners to delay conception ranges from 8 weeks to 6 months depending upon local transmission and presence of symptoms. For those who are not trying to become pregnant or who want to delay pregnancy because of Zika concerns or exposures, we should offer the full range of contraceptive options and work with each patient to optimize her contraceptive selection, based on her individual preferences, goals, and needs. Finally, women should be counseled to avoid transmission from sex by choosing to not have sex or by using a condom with each act of sex with a partner who may have been exposed to Zika.

Our understanding of Zika infection is rapidly evolving. It will be particularly important for us to stay current on this issue. Providers can access up-to-date information about Zika, provider updates, patient information, posters and other information about the emergency response from the CDC’s website at www.cdc.gov/zika/index.html.

There are several tools available for guidance in these conversations. On July 1, 2016, the Office of Population Affairs released a toolkit for Providing Family Planning Care for Non-Pregnant Women and Men of Reproductive Age in the Context of Zika. It is available online at: www.hhs.gov/opa/news#toolkit.

The CDC also offers comprehensive guidance on providing contraception. Providers can access the Medical Eligibility Criteria for Contraceptive Use, the Selected Practice Recommendations for Contraceptive Use, and Providing Quality Family Planning Services, all of which are available on the CDC website.

Dr. Kottke is an associate professor in the department of gynecology and obstetrics at Emory University in Atlanta, Georgia. She is the director of the Jane Fonda Center at Emory, which is involved in research and program development focused on adolescent sexual and reproductive health. She also serves as the medical consultant for the state of Georgia’s Family Planning Program. Dr. Kottke reported that she is a Nexplanon (Merck) trainer, is a consultant to CSL Behring, and serves on the advisory board for Evofem.

How do you treat a patient who doesn’t want to be treated?

It depends. If the problem is acne or a wart, then it’s all right to let it go.

Harriet, however, has HIV. And a facial basal cell carcinoma.

Now what?

Perhaps it still depends.

After showing me a red spot on her right cheek, Harriet put me on notice right away. “I don’t believe in unnecessary treatments,” she said.

I asked her what she meant.

“I’ve been HIV positive since the mid-1980s,” she said. “Last year, my doctor wanted to pump me full of those poisons. So I changed doctors.”

“What does your new doctor think?” I asked.

“My T-cell counts aren’t very good. He also thinks I should take those medicines, but I don’t see him much.

“I went to another dermatologist about a different problem. He got very angry at me, because I had called in advance to ask not to be seen by a resident. They told me that would be OK, but the resident showed up anyway. When the doctor also came in and I tried to explain, he threw me out of the clinic.”

By now, I’d gotten the picture: Harriet has her own ideas about things and is not about to take advice with which she doesn’t agree. What makes Harriet different is not that she ignores medical advice – people do that all the time – but that she comes right out and says so to the doctor’s face. Others wait till they get home.

So what do you do when a patient shows that he or she is ready to look you in the eye and turn you down flat?

One response is to leave the room in a huff. After all, who’s the expert here, and who’s trying to help whom?

That reaction is understandable, but if the doctor walks out, who is being helped? The patient, or the doctor?

There is, of course, another approach, which is to suppress professional ego considerations and ask:

1. What are the actual medical stakes? What is the worst that could happen if the patient refuses treatment?

2. What realistic options, if any, are there to change the patient’s mind?

3. Why is the patient behaving that way, anyway?

In Harriet’s case, what are the medical stakes? I am no HIV specialist, but how many patients who seroconverted in the 1980s are still around to consider their options? (Other such patients have told me their doctors really don’t understand how patients like them survived.) If Harriet is sexually inactive and does not try to donate blood, how sure are we that she isn’t better off doing nothing?

Besides, what other options are there to change her mind?

Before turning to my third question, I have to plan what to do if – when – the biopsy confirms my clinical diagnosis of basal cell. I will inform Harriet, and recommend Mohs surgery. Suppose she refuses and wants a lesser procedure, or no surgery at all. What next?

This happens. If the patient is elderly, and the lesion is not near a strategic organ, such as the eye, it may be acceptable just to watch the lesion. Some basal cells grow fast, others barely grow at all. If Harriet decides to do nothing, I could explain my preference – surgery – and her risks – lesion growth and bigger surgery later – and insist on seeing her every 2 months.

Which brings us to our third question: Why would Harriet act this way?

Two possibilities occur to me. The first is fear. Scared people often act aggressively. Calmed down, they relent.

The second is that Harriet is what the English call bloody minded; in other words, deliberately uncooperative.

Battling with the bloody minded is not helpful for anybody.

Negotiating with difficult people is much less gratifying than giving advice and being respectfully thanked for our efforts and expertise.

Sometimes, though, the best we can do is to swallow our professional pride, try to defuse what fear we can, and show that we will push only as hard as clinical risk truly justifies. This is not always easy to do but is often worth the effort. It may certainly be the best available alternative.

Harriet’s biopsy showed a basal cell. She readily agreed to surgery.

You never know.

Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University School of Medicine, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Dermatology News since January 2002. Write to him at [email protected].

How do you treat a patient who doesn’t want to be treated?

It depends. If the problem is acne or a wart, then it’s all right to let it go.

Harriet, however, has HIV. And a facial basal cell carcinoma.

Now what?

Perhaps it still depends.

After showing me a red spot on her right cheek, Harriet put me on notice right away. “I don’t believe in unnecessary treatments,” she said.

I asked her what she meant.

“I’ve been HIV positive since the mid-1980s,” she said. “Last year, my doctor wanted to pump me full of those poisons. So I changed doctors.”

“What does your new doctor think?” I asked.

“My T-cell counts aren’t very good. He also thinks I should take those medicines, but I don’t see him much.

“I went to another dermatologist about a different problem. He got very angry at me, because I had called in advance to ask not to be seen by a resident. They told me that would be OK, but the resident showed up anyway. When the doctor also came in and I tried to explain, he threw me out of the clinic.”

By now, I’d gotten the picture: Harriet has her own ideas about things and is not about to take advice with which she doesn’t agree. What makes Harriet different is not that she ignores medical advice – people do that all the time – but that she comes right out and says so to the doctor’s face. Others wait till they get home.

So what do you do when a patient shows that he or she is ready to look you in the eye and turn you down flat?

One response is to leave the room in a huff. After all, who’s the expert here, and who’s trying to help whom?

That reaction is understandable, but if the doctor walks out, who is being helped? The patient, or the doctor?

There is, of course, another approach, which is to suppress professional ego considerations and ask:

1. What are the actual medical stakes? What is the worst that could happen if the patient refuses treatment?

2. What realistic options, if any, are there to change the patient’s mind?

3. Why is the patient behaving that way, anyway?

In Harriet’s case, what are the medical stakes? I am no HIV specialist, but how many patients who seroconverted in the 1980s are still around to consider their options? (Other such patients have told me their doctors really don’t understand how patients like them survived.) If Harriet is sexually inactive and does not try to donate blood, how sure are we that she isn’t better off doing nothing?

Besides, what other options are there to change her mind?

Before turning to my third question, I have to plan what to do if – when – the biopsy confirms my clinical diagnosis of basal cell. I will inform Harriet, and recommend Mohs surgery. Suppose she refuses and wants a lesser procedure, or no surgery at all. What next?

This happens. If the patient is elderly, and the lesion is not near a strategic organ, such as the eye, it may be acceptable just to watch the lesion. Some basal cells grow fast, others barely grow at all. If Harriet decides to do nothing, I could explain my preference – surgery – and her risks – lesion growth and bigger surgery later – and insist on seeing her every 2 months.

Which brings us to our third question: Why would Harriet act this way?

Two possibilities occur to me. The first is fear. Scared people often act aggressively. Calmed down, they relent.

The second is that Harriet is what the English call bloody minded; in other words, deliberately uncooperative.

Battling with the bloody minded is not helpful for anybody.

Negotiating with difficult people is much less gratifying than giving advice and being respectfully thanked for our efforts and expertise.

Sometimes, though, the best we can do is to swallow our professional pride, try to defuse what fear we can, and show that we will push only as hard as clinical risk truly justifies. This is not always easy to do but is often worth the effort. It may certainly be the best available alternative.

Harriet’s biopsy showed a basal cell. She readily agreed to surgery.

You never know.

Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University School of Medicine, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Dermatology News since January 2002. Write to him at [email protected].

How do you treat a patient who doesn’t want to be treated?

It depends. If the problem is acne or a wart, then it’s all right to let it go.

Harriet, however, has HIV. And a facial basal cell carcinoma.

Now what?

Perhaps it still depends.

After showing me a red spot on her right cheek, Harriet put me on notice right away. “I don’t believe in unnecessary treatments,” she said.

I asked her what she meant.

“I’ve been HIV positive since the mid-1980s,” she said. “Last year, my doctor wanted to pump me full of those poisons. So I changed doctors.”

“What does your new doctor think?” I asked.

“My T-cell counts aren’t very good. He also thinks I should take those medicines, but I don’t see him much.

“I went to another dermatologist about a different problem. He got very angry at me, because I had called in advance to ask not to be seen by a resident. They told me that would be OK, but the resident showed up anyway. When the doctor also came in and I tried to explain, he threw me out of the clinic.”

By now, I’d gotten the picture: Harriet has her own ideas about things and is not about to take advice with which she doesn’t agree. What makes Harriet different is not that she ignores medical advice – people do that all the time – but that she comes right out and says so to the doctor’s face. Others wait till they get home.

So what do you do when a patient shows that he or she is ready to look you in the eye and turn you down flat?

One response is to leave the room in a huff. After all, who’s the expert here, and who’s trying to help whom?

That reaction is understandable, but if the doctor walks out, who is being helped? The patient, or the doctor?

There is, of course, another approach, which is to suppress professional ego considerations and ask:

1. What are the actual medical stakes? What is the worst that could happen if the patient refuses treatment?

2. What realistic options, if any, are there to change the patient’s mind?

3. Why is the patient behaving that way, anyway?

In Harriet’s case, what are the medical stakes? I am no HIV specialist, but how many patients who seroconverted in the 1980s are still around to consider their options? (Other such patients have told me their doctors really don’t understand how patients like them survived.) If Harriet is sexually inactive and does not try to donate blood, how sure are we that she isn’t better off doing nothing?

Besides, what other options are there to change her mind?

Before turning to my third question, I have to plan what to do if – when – the biopsy confirms my clinical diagnosis of basal cell. I will inform Harriet, and recommend Mohs surgery. Suppose she refuses and wants a lesser procedure, or no surgery at all. What next?

This happens. If the patient is elderly, and the lesion is not near a strategic organ, such as the eye, it may be acceptable just to watch the lesion. Some basal cells grow fast, others barely grow at all. If Harriet decides to do nothing, I could explain my preference – surgery – and her risks – lesion growth and bigger surgery later – and insist on seeing her every 2 months.

Which brings us to our third question: Why would Harriet act this way?

Two possibilities occur to me. The first is fear. Scared people often act aggressively. Calmed down, they relent.

The second is that Harriet is what the English call bloody minded; in other words, deliberately uncooperative.

Battling with the bloody minded is not helpful for anybody.

Negotiating with difficult people is much less gratifying than giving advice and being respectfully thanked for our efforts and expertise.

Sometimes, though, the best we can do is to swallow our professional pride, try to defuse what fear we can, and show that we will push only as hard as clinical risk truly justifies. This is not always easy to do but is often worth the effort. It may certainly be the best available alternative.

Harriet’s biopsy showed a basal cell. She readily agreed to surgery.

You never know.

Dr. Rockoff practices dermatology in Brookline, Mass. He is on the clinical faculty at Tufts University School of Medicine, Boston, and has taught senior medical students and other trainees for 30 years. Dr. Rockoff has contributed to the Under My Skin column in Dermatology News since January 2002. Write to him at [email protected].