Patient & Survivor Care

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

Survivors of childhood Hodgkin lymphoma have a 14-fold greater risk for second cancers, compared with the general population, according to newly published data.

The subsequent malignant neoplasms (SMNs) tend to follow specific patterns depending on the patient’s age at treatment, sex, treatment modality, and body region treated.

And although the risk of SMNs appears to be somewhat lower for patients treated in more recent decades, it is still significantly elevated, compared with that of the general population, according to Anna S. Holmqvist, MD, PhD, from Lund University (Sweden), and her colleagues.

“A major goal of the current study was to develop evidence with which to guide the screening of survivors of HL for the development of [solid] SMNs,” the investigators wrote in Cancer.

They examined at data from the Late Effects Study Group, a multinational cohort of patients aged 16 years or younger who were treated for Hodgkin lymphoma and other cancers from 1955 to 1986.

The current report is the third update from an expanded cohort, including data on 1,136 patients with a median follow-up of 26.6 years. The median patient age at diagnosis was 11 years and the patients were followed for 23,212 person-years following the Hodgkin lymphoma diagnosis.

In all, 162 patients developed a total of 196 solid SMNs, including breast cancer in 54 patients, basal cell carcinoma in 34 patients, thyroid cancer in 30, colorectal cancer in 15, lung cancer in 11, other malignancies in 40, and disease site not available in 12 patients.

The cumulative incidence of any solid SMN 40 years after a diagnosis of Hodgkin lymphoma was 26.4%. The standardized incidence ratio for the entire cohort was 14.0, compared with the general population as derived from the Surveillance, Epidemiology and End Results database.

Predisposing factors for breast cancer in females included a Hodgkin lymphoma diagnosis from the ages of 10-16 years, and treatment with radiotherapy to the chest.

The patients at highest risk for subsequent development of lung cancer were males treated with chest radiotherapy before age 10 years. Those at highest risk for colorectal cancer were males and females who had received abdominal/pelvic radiotherapy and high-dose alkylating agents. Patients at highest risk for thyroid cancers were females who had been treated with radiotherapy to the neck before the age of 10.

The cumulative incidence for breast cancer by age 50 years for those at highest risk was 45.3%. The respective cumulative incidences for lung, colorectal, and thyroid cancers by age 50 were 4.2%, 9.5%, and 17.3%.

The investigators noted that patients treated more recently are likely to have received lower doses and volumes of radiotherapy, compared with patients treated in 1970s and earlier. “However, for the cohort of patients treated between 1955 and 1986, it is clear that continued surveillance for [solid] SMNs is essential because their risk continues to increase as these survivors enter their fourth and subsequent decades of life.”

No specific funding source for the study was reported. The authors made no financial disclosures.
 

SOURCE: Holmqvist AS et al. Cancer. 2018 Dec 17. doi: 10.1002/cncr.31807.

SAN DIEGO – When it comes to aggressive care at the end of life, hematologists stand alone.

Hematology patients are more likely than are other patients to undergo chemotherapy and visit emergency departments and intensive care units when they’re near death, and they’re less likely to be referred for palliative care, according to David Hui, MD, an oncologist and palliative care specialist at the MD Anderson Cancer Center in Houston.

An analysis at the center, for example, found that 43% of hematology cancer patients received chemotherapy within the last 30 days of life, compared with 14% of patients with solid tumors.

“That’s not a number we’re proud of,” Dr. Hui said at the annual meeting of the American Society of Hematology. “Ultimately, at the end of life, do we want our patients to be in this setting? There is room for improvement.”

The cancer center isn’t an outlier on this front, Dr. Hui said. Data from other institutions in the United States and internationally confirm that hematologic oncologists tend to provide more aggressive care at the end of a patient’s life, compared with other cancer specialists.

“If you’re one of those patients, this is a very big deal,” said Dr. Hui, especially in light of data that suggest hematology patients get fewer referrals to palliative care than do other cancer patients. “Oncologists are optimistic, and hematologic oncologists especially,” he said.

Dr. Hui led a 2014 study of 816 adult cancer patients who died while under care at MD Anderson Cancer Center during 6 months in 2009 and 2010 (Cancer. 2014 May 15; 120[10]:1572-8).

“We found that patients with hematological malignancies were more likely to have multiple emergency room visits, intensive care unit admissions and death, and cancer treatments in the last weeks of life compared to patients with solid tumors,” the study authors wrote. “We also identified a relative lack of palliative care involvement in hematologic patients.”

Specifically, hematology cancer patients were much more likely to get aggressive end-of-life care than were the other cancer patients (odds ratio, 6.63, P less than .001).

Dr. Hui had led an earlier study that looked at the same 816 cancer patients and found that 45% had received palliative care consultations. But the researchers also found that patients with hematologic malignancies had significantly fewer palliative care referrals, the longest time between an advanced cancer diagnosis and a palliative care consultation, and one of the largest numbers of medical team encounters – a median of 38 – before palliative care (Oncologist. 2012;17[12]:1574-80).

In light of these numbers, policies at MD Anderson Cancer Center “are evolving rapidly,” Dr. Hui said.

He urged colleagues to think about the wishes of their patients. “What do patients really want? Good symptom control, time with family, not being a burden, not a prolonging dying process, having a sense of control during the middle of the turmoil.”

Dr. Hui added that the attitudes of oncologists regarding palliative care can affect whether patients get timely referrals to consultations. He led a 2016 study that surveyed 182 oncologists about end-of-life care and found that “many oncologists have a favorable attitude toward EOL care; this, in turn, was associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care.”

However, “we found that hematologic oncology specialists expressed lower comfort levels compared with their solid tumor counterparts,” a finding that reflects the results of other studies, the study authors wrote (Oncologist. 2016 Sep;21[9]:1149-55).

The stigma surrounding palliative care is a sticking point, Dr. Hui said, and has sparked a “rebranding” effort. Negative feelings about palliative decrease when it’s called “supportive care,” he said, and the new term is being adopted worldwide.

Dr. Hui reported having no financial disclosures.

SAN DIEGO – When it comes to aggressive care at the end of life, hematologists stand alone.

Hematology patients are more likely than are other patients to undergo chemotherapy and visit emergency departments and intensive care units when they’re near death, and they’re less likely to be referred for palliative care, according to David Hui, MD, an oncologist and palliative care specialist at the MD Anderson Cancer Center in Houston.

An analysis at the center, for example, found that 43% of hematology cancer patients received chemotherapy within the last 30 days of life, compared with 14% of patients with solid tumors.

“That’s not a number we’re proud of,” Dr. Hui said at the annual meeting of the American Society of Hematology. “Ultimately, at the end of life, do we want our patients to be in this setting? There is room for improvement.”

The cancer center isn’t an outlier on this front, Dr. Hui said. Data from other institutions in the United States and internationally confirm that hematologic oncologists tend to provide more aggressive care at the end of a patient’s life, compared with other cancer specialists.

“If you’re one of those patients, this is a very big deal,” said Dr. Hui, especially in light of data that suggest hematology patients get fewer referrals to palliative care than do other cancer patients. “Oncologists are optimistic, and hematologic oncologists especially,” he said.

Dr. Hui led a 2014 study of 816 adult cancer patients who died while under care at MD Anderson Cancer Center during 6 months in 2009 and 2010 (Cancer. 2014 May 15; 120[10]:1572-8).

“We found that patients with hematological malignancies were more likely to have multiple emergency room visits, intensive care unit admissions and death, and cancer treatments in the last weeks of life compared to patients with solid tumors,” the study authors wrote. “We also identified a relative lack of palliative care involvement in hematologic patients.”

Specifically, hematology cancer patients were much more likely to get aggressive end-of-life care than were the other cancer patients (odds ratio, 6.63, P less than .001).

Dr. Hui had led an earlier study that looked at the same 816 cancer patients and found that 45% had received palliative care consultations. But the researchers also found that patients with hematologic malignancies had significantly fewer palliative care referrals, the longest time between an advanced cancer diagnosis and a palliative care consultation, and one of the largest numbers of medical team encounters – a median of 38 – before palliative care (Oncologist. 2012;17[12]:1574-80).

In light of these numbers, policies at MD Anderson Cancer Center “are evolving rapidly,” Dr. Hui said.

He urged colleagues to think about the wishes of their patients. “What do patients really want? Good symptom control, time with family, not being a burden, not a prolonging dying process, having a sense of control during the middle of the turmoil.”

Dr. Hui added that the attitudes of oncologists regarding palliative care can affect whether patients get timely referrals to consultations. He led a 2016 study that surveyed 182 oncologists about end-of-life care and found that “many oncologists have a favorable attitude toward EOL care; this, in turn, was associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care.”

However, “we found that hematologic oncology specialists expressed lower comfort levels compared with their solid tumor counterparts,” a finding that reflects the results of other studies, the study authors wrote (Oncologist. 2016 Sep;21[9]:1149-55).

The stigma surrounding palliative care is a sticking point, Dr. Hui said, and has sparked a “rebranding” effort. Negative feelings about palliative decrease when it’s called “supportive care,” he said, and the new term is being adopted worldwide.

Dr. Hui reported having no financial disclosures.

SAN DIEGO – When it comes to aggressive care at the end of life, hematologists stand alone.

Hematology patients are more likely than are other patients to undergo chemotherapy and visit emergency departments and intensive care units when they’re near death, and they’re less likely to be referred for palliative care, according to David Hui, MD, an oncologist and palliative care specialist at the MD Anderson Cancer Center in Houston.

An analysis at the center, for example, found that 43% of hematology cancer patients received chemotherapy within the last 30 days of life, compared with 14% of patients with solid tumors.

“That’s not a number we’re proud of,” Dr. Hui said at the annual meeting of the American Society of Hematology. “Ultimately, at the end of life, do we want our patients to be in this setting? There is room for improvement.”

The cancer center isn’t an outlier on this front, Dr. Hui said. Data from other institutions in the United States and internationally confirm that hematologic oncologists tend to provide more aggressive care at the end of a patient’s life, compared with other cancer specialists.

“If you’re one of those patients, this is a very big deal,” said Dr. Hui, especially in light of data that suggest hematology patients get fewer referrals to palliative care than do other cancer patients. “Oncologists are optimistic, and hematologic oncologists especially,” he said.

Dr. Hui led a 2014 study of 816 adult cancer patients who died while under care at MD Anderson Cancer Center during 6 months in 2009 and 2010 (Cancer. 2014 May 15; 120[10]:1572-8).

“We found that patients with hematological malignancies were more likely to have multiple emergency room visits, intensive care unit admissions and death, and cancer treatments in the last weeks of life compared to patients with solid tumors,” the study authors wrote. “We also identified a relative lack of palliative care involvement in hematologic patients.”

Specifically, hematology cancer patients were much more likely to get aggressive end-of-life care than were the other cancer patients (odds ratio, 6.63, P less than .001).

Dr. Hui had led an earlier study that looked at the same 816 cancer patients and found that 45% had received palliative care consultations. But the researchers also found that patients with hematologic malignancies had significantly fewer palliative care referrals, the longest time between an advanced cancer diagnosis and a palliative care consultation, and one of the largest numbers of medical team encounters – a median of 38 – before palliative care (Oncologist. 2012;17[12]:1574-80).

In light of these numbers, policies at MD Anderson Cancer Center “are evolving rapidly,” Dr. Hui said.

He urged colleagues to think about the wishes of their patients. “What do patients really want? Good symptom control, time with family, not being a burden, not a prolonging dying process, having a sense of control during the middle of the turmoil.”

Dr. Hui added that the attitudes of oncologists regarding palliative care can affect whether patients get timely referrals to consultations. He led a 2016 study that surveyed 182 oncologists about end-of-life care and found that “many oncologists have a favorable attitude toward EOL care; this, in turn, was associated with greater provision of primary palliative care and higher rates of referral to specialist palliative care.”

However, “we found that hematologic oncology specialists expressed lower comfort levels compared with their solid tumor counterparts,” a finding that reflects the results of other studies, the study authors wrote (Oncologist. 2016 Sep;21[9]:1149-55).

The stigma surrounding palliative care is a sticking point, Dr. Hui said, and has sparked a “rebranding” effort. Negative feelings about palliative decrease when it’s called “supportive care,” he said, and the new term is being adopted worldwide.

Dr. Hui reported having no financial disclosures.

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Young women with early breast cancer who undergo mastectomy instead of breast-conserving surgery have poorer quality of life in the longer term, according to investigators for a multicenter cross-sectional cohort study reported at the San Antonio Breast Cancer Symposium.

Women aged 40 or younger make up about 7% of all newly diagnosed cases of breast cancer in the United States, according to lead author, Laura S. Dominici, MD, of Dana-Farber/Brigham and Women’s Cancer Center and Harvard Medical School, Boston.

“Despite the fact that there is equivalent local-regional control with breast conservation and mastectomy, the rates of mastectomy and particularly bilateral mastectomy are increasing in young women, with a 10-fold increase seen from 1998 to 2011,” she noted in a press conference. “Young women are at particular risk for poorer psychosocial outcomes following a breast cancer diagnosis and in survivorship. However, little is known about the impact of surgery, particularly in the era of increasing bilateral mastectomy, on the quality of life of young survivors.”

Nearly three-fourths of the 560 young breast cancer survivors studied had undergone mastectomy, usually with some kind of reconstruction. Roughly 6 years later, compared with peers who had undergone breast-conserving surgery, women who had undergone unilateral or bilateral mastectomy had significantly poorer adjusted BREAST-Q scores for satisfaction with the appearance and feel of their breasts (beta, –8.7 and –9.3 points) and psychosocial well-being (–8.3 and –10.5 points). The latter also had poorer adjusted scores for sexual well-being (–8.1 points). Physical well-being, which captures aspects such as pain and range of motion, did not differ significantly by type of surgery.

“Local therapy decisions are associated with a persistent impact on quality of life in young breast cancer survivors,” Dr. Dominici concluded. “Knowledge of the potential long-term impact of surgery and quality of life is of critical importance for counseling young women about surgical decisions.”
 

Moving away from mastectomy

“The data are, to me anyway, more disconcerting when you consider the high mastectomy rate in this country relative to Europe, and this urge to have bilateral mastectomies, which, pardon the expression, is ridiculous in some cases because it doesn’t improve your outcome. And yet, it does have deleterious effects that last for years psychologically,” commented SABCS codirector and press conference moderator C. Kent Osborne, MD, who is director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “What can we do about that?” he asked.

“It’s a really challenging problem,” Dr. Dominici replied. “Part of what we are missing in the conversation that we have with our patients is this kind of information. We can certainly tell patients that the outcomes are equivalent, but if they don’t know that the long-term [quality of life] impact is potentially worse, then that may not affect their decision. The more prospective data that we generate to help us figure out which patients are going to have better or worse outcomes with these different types of surgery, the better we will be able to counsel patients with things that will be meaningful to them in the long run.”

The study was not designed to tease out the specific role of anxiety about a recurrence or a new breast cancer, which is a major driver of the decision to have mastectomy and also needs to be addressed during counseling, Dr. Dominici and Dr. Osborne agreed. “I think I spend more time talking patients out of bilateral mastectomy or mastectomy at all than anything,” he commented.
 

Study details

The women studied were participants in the prospective Young Women’s Breast Cancer Study (YWS) and had a mean age of 37 years at diagnosis. Most (86%) had stage 0-2 breast cancer. (Those with metastatic disease at diagnosis or a recurrence during follow-up were excluded.)

Overall, 52% of the women underwent bilateral mastectomy, 20% underwent unilateral mastectomy, and 28% underwent breast-conserving surgery, Dr. Dominici reported. Within the mastectomy group, most underwent implant-based reconstruction (69%) or flap reconstruction (12%), while some opted for no reconstruction (11%).

Multivariate analyses showed that, in addition to mastectomy, other significant predictors of poorer breast satisfaction were receipt of radiation therapy (beta, –7.5 points) and having a financially uncomfortable status as compared with a comfortable one (–5.4 points).

Additional significant predictors of poorer psychosocial well-being were receiving radiation (beta, –6.0 points), being financially uncomfortable (–7 points), and being overweight or obese (–4.2 points), and additional significant predictors of poorer sexual well-being were being financially uncomfortable (–6.8 points), being overweight or obese (–5.3 points), and having lymphedema a year after diagnosis (–3.8 points).

The only significant predictors of poorer physical health were financially uncomfortable status (beta, –4.8 points) and lymphedema (–6.4 points), whereas longer time since surgery (more than 5 years) predicted better physical health (+6.0 points), according to Dr. Dominici.

Age, race, marital status, work status, education level, disease stage, chemotherapy, and endocrine therapy did not significantly predict any of the outcomes studied.

“This was a one-time survey of women who were enrolled in an observational cohort study, and we know that preoperative quality of life likely drives surgical choices,” she commented, addressing the study’s limitations. “Our findings may have limited generalizability to a more diverse population in that the majority of our participants were white and of high socioeconomic status.”

Dr. Dominici disclosed that she had no conflicts of interest. The study was funded by the Agency for Healthcare Research and Quality, Susan G. Komen, the Breast Cancer Research Foundation, and The Pink Agenda.

SOURCE: Dominici LS et al. SABCS 2018, Abstract GS6-06,

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Data continue to underscore the benefits of lifestyle interventions in women with breast cancer, but questions remain about their effects on recurrence, according to Jennifer Ligibel, MD.

Findings from the EBBA-II trial as presented at the San Antonio Breast Cancer Symposium, for example, showed that exercise improves cardiorespiratory fitness in women with early breast cancer, and findings from the SUCCESS C study showed that breast cancer patients who completed a weight-loss intervention showed some improvements, compared with those who did not, said Dr. Ligibel of Dana-Farber Cancer Institute in Boston, who was the discussant for those and other lifestyle-intervention studies at the symposium.

SUCCESS C failed to show an overall reduction in breast cancer recurrence or survival, but weight loss among intervention-group participants was modest, and more than half of the participants dropped out of the study, so it’s hard to make any firm conclusions, she said.

Overall, the findings – in the context of what is already known about lifestyle interventions among women with breast cancer – provide “yet another reason to tell women that it’s important to exercise during treatment,” she said.

Vidyard Video

In this video interview, Dr. Ligibel discussed the studies and the implications of the findings, and also mentioned an ongoing study for which she is an investigator. In that study – the Breast Cancer Weight Loss study (BWEL) – adherence among the approximately 1,700 women enrolled has been high. “So we’re hoping that this study in a few years will give us a bit more information about the power of weight loss to potentially reduce recurrence.”

For now, the available data show that there are “lots of concrete benefits” associated with improving lifestyle in women with breast cancer, she said, noting that she tells all of her patients to live as healthy a lifestyle as possible, and especially to exercise.

[email protected]

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved for the treatment of overactive bladder, provides a new option for managing hot flashes in women who can’t use estrogen because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.

Susan London/MDedge News

Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium

But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.

The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.

The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.

Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.

“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
 

Treatment considerations

“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.

Susan London/MDedge News

“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.

His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”

As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.

It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.

“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
 

Study details

The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.

In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.

Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.

Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.

Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved for the treatment of overactive bladder, provides a new option for managing hot flashes in women who can’t use estrogen because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.

Susan London/MDedge News

Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium

But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.

The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.

The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.

Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.

“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
 

Treatment considerations

“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.

Susan London/MDedge News

“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.

His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”

As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.

It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.

“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
 

Study details

The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.

In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.

Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.

Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.

Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.

SAN ANTONIO – Oxybutynin (Ditropan), a drug approved for the treatment of overactive bladder, provides a new option for managing hot flashes in women who can’t use estrogen because of a history of or concern about breast cancer, suggests a phase 3 double-blind randomized controlled trial.

Susan London/MDedge News

Managing hot flashes in breast cancer survivors is important for ensuring their adherence to endocrine therapy, as about a third fail to complete the recommended 5- to 7-year course, in part because of side effects, Roberto A. Leon-Ferre, MD, of the Mayo Clinic, Rochester, Minn., reported at the San Antonio Breast Cancer Symposium

But many survivors cannot use estrogen because of hormone receptor–positive disease, and currently used nonhormonal alternatives have drawbacks. “Some of these agents interfere with the metabolic activation of tamoxifen, for example. There is also the association, unfortunately, of the taboo of taking antidepressants or anticonvulsants when you don’t have those diagnoses,” he said. In addition, a variety of nonpharmacologic options, such as black cohosh and vitamin E, have not proved any more effective than placebo.

The 150 women enrolled in the trial, ACCRU study SC-1603, were experiencing frequent, bothersome hot flashes and had a history of or concern about breast cancer. The 6-week reduction in a hot flash score capturing both frequency and severity was about 30% with placebo, 65% with oxybutynin 2.5 mg b.i.d., and 80% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose vs. placebo), with a difference emerging within 2 weeks. “These doses are on the lower end of the currently used doses for urinary incontinence,” Dr. Leon-Ferre noted, with that range extending up to 20 mg daily.

The oxybutynin groups also had significantly greater reductions in hot flash frequency alone and improvements in measures of quality of life such as sleep, work, and relations. The drug was well tolerated, with expected main side effects of dry mouth and difficulty urinating.

Despite the potential pitfalls of cross-trial comparisons, the magnitude of benefit with oxybutynin appeared to exceed that previously reported with clonidine, fluoxetine, citalopram, venlafaxine, and pregabalin, according to Dr. Leon-Ferre.

“Oxybutynin significantly improves hot flash frequency and severity. The use of oxybutynin, more importantly, is associated with a positive impact in several quality of life metrics. And toxicity was acceptable,” he said. “While the two oxybutynin doses were not formally compared, 5 mg twice daily appears to be more effective.”
 

Treatment considerations

“What is your current strategy for using this variety of drugs?” asked SABCS codirector and press conference moderator C. Kent Osborne, MD, director of the Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston. “Also, acupuncture has been shown to work in several randomized trials,” he noted.

Susan London/MDedge News

“Before this study, we had been primarily using citalopram or venlafaxine as our first drug intervention. We typically favored venlafaxine for patients who are taking tamoxifen due to the concern about interaction with the CYP2D6 inhibitors,” Dr. Leon-Ferre replied. Oxybutynin is an attractive alternative here because patients can stop it abruptly if they want, whereas venlafaxine may require a lengthy period of tapering and weaning.

His institution doesn’t have a structured acupuncture program. “We do have acupuncturists, but they have to follow a specific program, it’s not any acupuncture. But we often recommend that patients pursue it if they have access to it,” he explained. “With the results of this particular study, we have become more keen on using oxybutynin. As a matter of fact, many of the patients who enrolled in this study decided to continue [or start] it after it had been revealed whether they were taking it or the placebo.”

As with all therapies, it is important to match the therapy to the patient, Dr. Leon-Ferre cautioned. “I can tell you that we have been using oxybutynin, but one has to be cautious about which patients to select for this because this is an anticholinergic drug. We were very careful about not including patients who had taken other potent anticholinergic drugs because these medications can lead to confusion episodes and altered mental status, particularly in more elderly patients and patients who suffer from polypharmacy and take many medications that start interacting with each other.” Another contraindication is urinary retention.

It is also noteworthy that women in the trial received just 6 weeks of oxybutynin therapy, as there has been some concern that extended use of anticholinergics can lead to memory issues.

“With those caveats, I think that if we have an informed decision, we could prescribe oxybutynin to patients,” Dr. Leon-Ferre said. “But ideally, I would say try to use it for a shorter rather than longer period of time.”
 

Study details

The women randomized in ACCRU study SC-1603 had had hot flashes for at least 30 days and were experiencing at least 28 of them each week. Concurrent stable-dose antidepressants, gabapentin, and pregabalin were allowed, whereas concurrent potent anticholinergics were not. Two-thirds of the women were on tamoxifen or an aromatase inhibitor.

In addition to the dramatic reduction in hot flash scores seen with oxybutynin, the drug was associated with marked reductions in hot flash frequency: 30% with placebo versus 60% with oxybutynin 2.5 mg b.i.d. and 75% with oxybutynin 5 mg b.i.d. (P less than .01 across groups and for each dose compared with placebo), Dr. Leon-Ferre reported.

Most of the 10 domains on the Hot Flash-Related Daily Interference Scale were significantly more improved with both doses of oxybutynin relative to placebo. The exceptions were mood and life enjoyment, which were significantly more improved only with the higher dose, and concentration and sexuality, which were not significantly more improved with either dose.

Both doses of oxybutynin were overall well tolerated, according to Dr. Leon-Ferre. Each was associated with higher incidence of dry mouth, abdominal pain, and difficulty urinating relative to placebo, as expected from what is known about the drug. The higher dose had a greater incidence of dry eyes, episodes of confusion, diarrhea, and headache.

Dr. Leon-Ferre disclosed that he had no conflicts of interest. The study was funded by the Breast Cancer Research Foundation.

SOURCE: Leon-Ferre RA et al. SABCS 2018 Abstract GS6-02.

SAN DIEGO – Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the Phase 3 ADAM VTE trial.

The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.

The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
 

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,

pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT) – 48% and 47%, respectively
• PE only – 44% and 39%, respectively
• PE with DVT – 12% in both arms
• DVT only – 37% and 35%, respectively
• Lower extremity DVT – 31% and 34%, respectively
• Upper extremity DVT – 17% and 14%, respectively
• Cerebral venous thrombosis (VT) – 1% and 0%, respectively
• Splanchnic VT – 8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
 

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).

“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

[email protected]

SOURCE: McBane RD et al. ASH 2018, Abstract 421.

SAN DIEGO – Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the Phase 3 ADAM VTE trial.

The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.

The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
 

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,

pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT) – 48% and 47%, respectively
• PE only – 44% and 39%, respectively
• PE with DVT – 12% in both arms
• DVT only – 37% and 35%, respectively
• Lower extremity DVT – 31% and 34%, respectively
• Upper extremity DVT – 17% and 14%, respectively
• Cerebral venous thrombosis (VT) – 1% and 0%, respectively
• Splanchnic VT – 8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
 

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).

“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

[email protected]

SOURCE: McBane RD et al. ASH 2018, Abstract 421.

SAN DIEGO – Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the Phase 3 ADAM VTE trial.

The rates of major bleeding and clinically relevant nonmajor bleeding in patients who received apixaban were similar to those in patients who received dalteparin. However, the rate of VTE recurrence was significantly lower with apixaban than it was with dalteparin.

“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane II, MD, of the Mayo Clinic in Rochester, Minn., at the annual meeting of the American Society of Hematology.

The trial included 300 adults (aged 18 years and older) with active cancer and acute VTE who were randomized to receive apixaban (n = 150) or dalteparin (n = 150). The dose and schedule for oral apixaban was 10 mg twice daily for 7 days followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month followed by 150 IU/kg daily for 6 months. Among the patients in the study, 145 patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.

Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
 

Patient characteristics

Baseline characteristics were similar between the treatment arms. The mean age was 64 years in both arms, and roughly half of patients in both arms were female. Hematologic malignancies were present in 9% of patients in the apixaban arm and 11% in the dalteparin arm. Others included lung, colorectal,

pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.

Of patients in the study, 65% of those in the apixaban arm and 66% in the dalteparin arm had distant metastasis, and 74% of patients in both arms were receiving chemotherapy while on study.

Patients had the following qualifying thrombotic events:

• Any pulmonary embolism (PE) – 55% of patients in the apixaban arm and 51% in the dalteparin arm
• Any deep vein thrombosis (DVT) – 48% and 47%, respectively
• PE only – 44% and 39%, respectively
• PE with DVT – 12% in both arms
• DVT only – 37% and 35%, respectively
• Lower extremity DVT – 31% and 34%, respectively
• Upper extremity DVT – 17% and 14%, respectively
• Cerebral venous thrombosis (VT) – 1% and 0%, respectively
• Splanchnic VT – 8% and 18%, respectively.

Bleeding, thrombosis, and death

The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P = .14).

A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P = .88).

The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P = .03).

The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n = 4) or arm (n = 2) VTE, PE (n = 1), or splanchnic VT (n = 2).

One patient in each arm (0.7%) had arterial thrombosis.

There was no significant difference in cumulative mortality between the treatment arms (hazard ratio, 1.40; P = .3078).
 

Satisfaction and discontinuation

Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to be concerned about excessive bruising, find anticoagulant treatment a burden or difficult to carry out, or say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.

However, apixaban-treated patients were less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence, while the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.

In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group – 15% and 4%, respectively (P = .0012).

“Apixaban was well tolerated with superior patient safety satisfaction, as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”

This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.

[email protected]

SOURCE: McBane RD et al. ASH 2018, Abstract 421.

SAN FRANCISCO – Empiric antibiotic therapy for febrile neutropenia, a common and life-threatening complication of chemotherapy, hasn’t really changed much in 20 years, according to Alison Freifeld, MD, director of the section of oncology infectious diseases at the University of Nebraska, Omaha.

luchschen/Thinkstock

Antibiotic resistance has become a major problem over that time. Multidrug-resistant, gram-negative blood stream infections are not uncommon, particularly with extended-spectrum, beta-lactamase–producing Escherichia coli and Klebsiella pneumoniae. Carbapenemase-producing Enterobacteriaceae are also on the rise, among others.

“Our standard empiric antibiotics” – ceftazidime, cefepime, piperacillin/tazobactam, and carbapenems – “are generally not active against these organisms, putting us in a major dilemma about what to do” with patients who have them, Dr. Freifeld said.

“Our goal at the moment is to unpack this ship, take some of these loads of antibiotics off, and figure out how we can more effectively bridge the gap between risk factors and outcomes, with fewer and more stringently applied targeted antibiotics,” she said at ID Week, an annual scientific meeting on infectious diseases.

Dr. Freifeld shared her advice at the meeting on what to do as that plays out. The main driver is to protect the remaining potency of current antibiotics without sacrificing patient care while also keeping new options in reserve for the sickest patients, so “we do not overuse these precious commodities.”

For one thing, it’s okay to shorten treatment – traditionally around 2 weeks, until the absolute neutrophil count (ANC) tops 500 cells/mcg – once the fever abates and cultures turn negative, even if the ANC remains low.

A recent trial put the approach to the test. A total of 78 patients had their antibiotics stopped after they had been free of fever for 72 hours, with normal vital signs and no other signs of infection; 79 in the control group had usual care, continuing treatment until their ANC recovered.

Early withdrawal shortened treatment by about 3 days and there were no statistically significant differences in mortality, with one death in the short-arm group and three in the long-arm group. Over half of the patients in the short-arm group were neutropenic when antibiotics were discontinued.

Serious adverse events, meanwhile, were far less common in the short-arm group (18 vs. 38). The take-home lesson is that “interventions to shorten duration of empiric antibiotics are safe and effective and important to implement now,” Dr. Freifeld said (Lancet Haematol. 2017 Dec;4(12):e573-83).

Also, “use escalation and deescalation approaches,” she said. The basic idea is to begin with monotherapy – cefepime or piperacillin/tazobactam – in uncomplicated cases, bumped up as necessary, and, in complicated cases, to start with broad, multidrug regimens, deescalated as culture reports and other information comes in (Haematologica. 2013 Dec;98(12):1826-35).

Finally, fluoroquinolone prophylaxis, “once considered the wonder of the world,” Dr. Freifeld said, needs to be limited to the highest-risk patients, particularly those with neutropenia expected to last a week or more. It does seem to lower the rates of fever and bloodstream infections, but recent investigations have shown no mortality benefit, and fluoroquinolone prophylaxis makes patients more likely to be colonized by multidrug-resistant bacteria. Many centers have opted against it, even in higher-risk patients (J Infect. 2018 Jan;76(1):20-37).

Dr. Freifeld serves on a data adjudication committee for Merck, and reported research support from the company.

[email protected]

SAN FRANCISCO – Empiric antibiotic therapy for febrile neutropenia, a common and life-threatening complication of chemotherapy, hasn’t really changed much in 20 years, according to Alison Freifeld, MD, director of the section of oncology infectious diseases at the University of Nebraska, Omaha.

luchschen/Thinkstock

Antibiotic resistance has become a major problem over that time. Multidrug-resistant, gram-negative blood stream infections are not uncommon, particularly with extended-spectrum, beta-lactamase–producing Escherichia coli and Klebsiella pneumoniae. Carbapenemase-producing Enterobacteriaceae are also on the rise, among others.

“Our standard empiric antibiotics” – ceftazidime, cefepime, piperacillin/tazobactam, and carbapenems – “are generally not active against these organisms, putting us in a major dilemma about what to do” with patients who have them, Dr. Freifeld said.

“Our goal at the moment is to unpack this ship, take some of these loads of antibiotics off, and figure out how we can more effectively bridge the gap between risk factors and outcomes, with fewer and more stringently applied targeted antibiotics,” she said at ID Week, an annual scientific meeting on infectious diseases.

Dr. Freifeld shared her advice at the meeting on what to do as that plays out. The main driver is to protect the remaining potency of current antibiotics without sacrificing patient care while also keeping new options in reserve for the sickest patients, so “we do not overuse these precious commodities.”

For one thing, it’s okay to shorten treatment – traditionally around 2 weeks, until the absolute neutrophil count (ANC) tops 500 cells/mcg – once the fever abates and cultures turn negative, even if the ANC remains low.

A recent trial put the approach to the test. A total of 78 patients had their antibiotics stopped after they had been free of fever for 72 hours, with normal vital signs and no other signs of infection; 79 in the control group had usual care, continuing treatment until their ANC recovered.

Early withdrawal shortened treatment by about 3 days and there were no statistically significant differences in mortality, with one death in the short-arm group and three in the long-arm group. Over half of the patients in the short-arm group were neutropenic when antibiotics were discontinued.

Serious adverse events, meanwhile, were far less common in the short-arm group (18 vs. 38). The take-home lesson is that “interventions to shorten duration of empiric antibiotics are safe and effective and important to implement now,” Dr. Freifeld said (Lancet Haematol. 2017 Dec;4(12):e573-83).

Also, “use escalation and deescalation approaches,” she said. The basic idea is to begin with monotherapy – cefepime or piperacillin/tazobactam – in uncomplicated cases, bumped up as necessary, and, in complicated cases, to start with broad, multidrug regimens, deescalated as culture reports and other information comes in (Haematologica. 2013 Dec;98(12):1826-35).

Finally, fluoroquinolone prophylaxis, “once considered the wonder of the world,” Dr. Freifeld said, needs to be limited to the highest-risk patients, particularly those with neutropenia expected to last a week or more. It does seem to lower the rates of fever and bloodstream infections, but recent investigations have shown no mortality benefit, and fluoroquinolone prophylaxis makes patients more likely to be colonized by multidrug-resistant bacteria. Many centers have opted against it, even in higher-risk patients (J Infect. 2018 Jan;76(1):20-37).

Dr. Freifeld serves on a data adjudication committee for Merck, and reported research support from the company.

[email protected]

SAN FRANCISCO – Empiric antibiotic therapy for febrile neutropenia, a common and life-threatening complication of chemotherapy, hasn’t really changed much in 20 years, according to Alison Freifeld, MD, director of the section of oncology infectious diseases at the University of Nebraska, Omaha.

luchschen/Thinkstock

Antibiotic resistance has become a major problem over that time. Multidrug-resistant, gram-negative blood stream infections are not uncommon, particularly with extended-spectrum, beta-lactamase–producing Escherichia coli and Klebsiella pneumoniae. Carbapenemase-producing Enterobacteriaceae are also on the rise, among others.

“Our standard empiric antibiotics” – ceftazidime, cefepime, piperacillin/tazobactam, and carbapenems – “are generally not active against these organisms, putting us in a major dilemma about what to do” with patients who have them, Dr. Freifeld said.

“Our goal at the moment is to unpack this ship, take some of these loads of antibiotics off, and figure out how we can more effectively bridge the gap between risk factors and outcomes, with fewer and more stringently applied targeted antibiotics,” she said at ID Week, an annual scientific meeting on infectious diseases.

Dr. Freifeld shared her advice at the meeting on what to do as that plays out. The main driver is to protect the remaining potency of current antibiotics without sacrificing patient care while also keeping new options in reserve for the sickest patients, so “we do not overuse these precious commodities.”

For one thing, it’s okay to shorten treatment – traditionally around 2 weeks, until the absolute neutrophil count (ANC) tops 500 cells/mcg – once the fever abates and cultures turn negative, even if the ANC remains low.

A recent trial put the approach to the test. A total of 78 patients had their antibiotics stopped after they had been free of fever for 72 hours, with normal vital signs and no other signs of infection; 79 in the control group had usual care, continuing treatment until their ANC recovered.

Early withdrawal shortened treatment by about 3 days and there were no statistically significant differences in mortality, with one death in the short-arm group and three in the long-arm group. Over half of the patients in the short-arm group were neutropenic when antibiotics were discontinued.

Serious adverse events, meanwhile, were far less common in the short-arm group (18 vs. 38). The take-home lesson is that “interventions to shorten duration of empiric antibiotics are safe and effective and important to implement now,” Dr. Freifeld said (Lancet Haematol. 2017 Dec;4(12):e573-83).

Also, “use escalation and deescalation approaches,” she said. The basic idea is to begin with monotherapy – cefepime or piperacillin/tazobactam – in uncomplicated cases, bumped up as necessary, and, in complicated cases, to start with broad, multidrug regimens, deescalated as culture reports and other information comes in (Haematologica. 2013 Dec;98(12):1826-35).

Finally, fluoroquinolone prophylaxis, “once considered the wonder of the world,” Dr. Freifeld said, needs to be limited to the highest-risk patients, particularly those with neutropenia expected to last a week or more. It does seem to lower the rates of fever and bloodstream infections, but recent investigations have shown no mortality benefit, and fluoroquinolone prophylaxis makes patients more likely to be colonized by multidrug-resistant bacteria. Many centers have opted against it, even in higher-risk patients (J Infect. 2018 Jan;76(1):20-37).

Dr. Freifeld serves on a data adjudication committee for Merck, and reported research support from the company.

[email protected]

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN DIEGO – Tom Brokaw has devoted his life to openness and transparency. But he kept mum about a big story that only he could fully tell – his diagnosis of multiple myeloma. He alerted his bosses and a few loved ones but otherwise kept his condition secret even as he struggled to walk and navigate stairs.

Courtesy American Society of Hematology

“I didn’t want to be Tom Brokaw, cancer victim,” he said at the annual meeting of the American Society of Hematology. But he did decide to go public in a big way and he said he doesn’t regret it. “I’m kind of the multiple myeloma poster boy.”

Since opening up about myeloma, “I have learned more about life and medicine, and kindness and the extraordinary strength of this country, than I have in all my other experiences,” he said. “I can say, oddly enough, at age 78 about to be 79, that having multiple myeloma has been a kind of privilege for me.”

Mr. Brokaw is best known as the longtime anchor of “NBC Nightly News” and author of “The Greatest Generation,” about the American experience in World War II. He was diagnosed with multiple myeloma in 2013 and revealed his condition publicly in 2014.

In 2016, he described his treatment in a New York Times commentary: “...three years of chemotherapy, a spinal operation that cost me three inches of height, monthly infusions of bone supplements, and drugs to prevent respiratory infection.” He also described fatigue, bone damage, and a 24-pill-a-day regimen.

In his presentation at ASH, Mr. Brokaw detailed the adjustment of having to slow down after an active life as a cyclist and outdoorsman. “I’m not going to go down the street with a cane. My birth certificate says I’m 78 years old, but I still think I’m 38, anchoring the news.”

When asked how his care could have been improved, Mr. Brokaw said there could have been more focus on the physical effects of multiple myeloma on his body. “There was so much concentration on the disease itself that I don’t think I got as much as I needed regarding the radiant effects.”

At one point, he fell while running with his dog, and developed an infection in a cavity in his elbow. Still, he refused to cancel a flight to Washington, D.C., for an interview with the secretary of defense. The infection got worse, soaking his shirt with leakage, and when he returned “they slammed me into intensive care.”

He got a stern instruction that “you can’t do this anymore,” and he responded with an “ohh-kay.”

“It’s the anchorman in me. You get used to doing what you want to do. But I have to be much more careful about what I do and when I do it,” he said.

Now, Mr. Brokaw still struggles to follow advice about risks such as flying. But he remains active as a speaker, a special correspondent for NBC, and an author. “By and large,” he said, “I’m getting along OK. I’m grateful for that.”

SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
 

The overall change in VO_2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.

Among patients receiving chemotherapy, the VO_2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.

Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m², and a mean VO_2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO_2max at baseline.


They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.

Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.

In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.

“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.

Dr. Thune reported having no disclosures.

SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
 

The overall change in VO_2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.

Among patients receiving chemotherapy, the VO_2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.

Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m², and a mean VO_2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO_2max at baseline.


They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.

Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.

In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.

“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.

Dr. Thune reported having no disclosures.

SAN ANTONIO – A tailored 12-month exercise program during adjuvant breast cancer treatment appears to protect cardiovascular function, particularly in patients receiving chemotherapy, according to findings from the randomized EBBA-II trial.
 

The overall change in VO_2max at 12 months was +0.3% in 271 patients randomized to the intervention group, compared with –8.9% in 274 patients in the “usual care” control group, Inger Thune, MD, PhD, said at the San Antonio Breast Cancer Symposium.

Among patients receiving chemotherapy, the VO_2max change at 12 months was +1.6% in 120 patients in the intervention group, compared with –2.76% in 122 patients in the control group, said Dr. Thune of the Cancer Center at Oslo University Hospital.

Study participants were women aged 18-75 years (mean of 55 years at diagnosis) with stage I-II breast cancer, mean body mass index of 25 kg/m², and a mean VO_2max before surgery of 31.5 mL/kg per minute. The intervention group entered a 12-month individualized exercise program 2-3 weeks after surgery based on their own VO_2max at baseline.


They met for training sessions in groups of 10-12 women for 60 minutes twice weekly over the 12-month study period, and were also told to perform at least 120 minutes of exercise at home for a total of 240 minutes of exercise weekly.

Of note, the adherence rate among participants was encouragingly high at about 90%, she said, adding that the findings strongly support tailored exercise during adjuvant breast cancer treatment, as such an intervention appears to counteract declines in cardiovascular function – particularly in those receiving chemotherapy.

In this video interview, Dr. Thune further discussed the study design, implications of the findings, and future directions.

“Cardiovascular morbidity is so important for our breast cancer patients that I think that it’s time to have physical activity [and] physical function as a main interest for all clinicians dealing with breast cancer patients,” she said.

Dr. Thune reported having no disclosures.