Patient & Survivor Care

SAN DIEGO – Of the many scales at a clinician’s disposal to measure acute pain, the three most commonly used are the Numerical Rating Scale, the Verbal Rating Scale, and the Visual Analog Scale, Dr. Jeffrey A. Stone said at the annual meeting of the Society of Neurointerventional Surgery.

"All of these scales have been shown to be statistically reliable and valid," said Dr. Stone, associate professor of neurointerventional surgery in the radiology department at the Mayo Clinic, Jacksonville, Fla. In his clinical experience, most patients prefer the Numerical Rating Scale (NRS) and the Verbal Rating Scale (VRS) because they are easy to use. "The other advantage is that these can be conducted by telephone or electronic diaries," he said.

The NRS is a familiar and commonly used 0-10 scale, where 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, and 7-10 = severe pain. "If patients tell you, ‘I’m a 5 out of 10,’ that can be difficult to gauge, particularly in the elderly," Dr. Stone said. "The VRS, a four-scale system ranging from no pain up to severe pain, is somewhat simpler and correlates well with the NRS."

With the Visual Analog Scale, patients are asked to make a vertical slash on a 100-mm line to denote their level of pain. "I use this scale a lot, but it can be cumbersome, particularly with follow-up," he said.

Factors to consider in the backdrop of pain intensity include rescue analgesics, which may be prescribed by other physicians for sleep or anxiety, or may be used to prevent pain from increased activity or to treat unrelated pain. "Another factor is concomitant pain treatments, such as acupuncture and chiropractic treatments," Dr. Stone said. "In addition, patients enrolled in the placebo group of a clinical trial are generally expected to have more pain medication use compared with those in an efficacious treatment group."

Other distinct components of pain include pain sensation and pain affect. Pain sensation "is the quality of the pain, such as burning, throbbing, or sharp pain versus dull pain," Dr. Stone said. "There are also temporal aspects to pain, such as variability of intensity over time; time to onset of meaningful pain relief; durability of pain relief; and the frequency, duration, and intensity of pain episodes. Pain affect is the mental distress caused by the pain."

Global pain assessments for pain sensation and pain affect include a modification of the McGill Pain Questionnaire (MPQ), known as the short-form MPQ, and the Brief Pain Inventory (BPI), which was adapted from the Wisconsin Brief Pain Questionnaire. The short-form MPQ contains 15 sensory and affective descriptors, while the BPI "does a much better job measuring the temporal aspect of pain and is often used in conjunction with the short-form MPQ," Dr. Stone said.

Two other core pain outcome domains are physical function and emotional function. Effective outcome measures for these domains include the Oswestry Disability Index (ODI), the Short Form-36 (SF-36), the Roland-Morris Disability Questionnaire (RMQ) and the Pain Disability Index (PDI).

The ODI, a 10-item questionnaire, "has been used in many pain trials," he said. "It looks at pain intensity but also other things such as lifting, the ability to walk, social life, sexual activity, and sleep cycle. It is a very accurate way to look at a patient’s global disability from pain."

He described the SF-36 as "a little bit more cumbersome for patients to complete" in measuring physical and emotional function. This tool provides an eight-scale profile of functional health and well-being scores, as well as a psychometric-based physical and mental health summary.

The 24-item RMQ consists of yes/no questions intended to measure self-perceived disability, while the 7-question PDI measures pain interference in physical and psychosocial role performance.

In a later interview, Dr. Stone said that the NRS, VRS, and VAS instruments can be used in hospitalized patients. Outcome measures such as the ODI and the RMQ "would not be very useful, as they ask many functional questions such as sex life [and] activity level, which would not be applicable to a hospitalized patient."

Dr. Stone said that he had no relevant financial disclosures to make.

SAN DIEGO – Of the many scales at a clinician’s disposal to measure acute pain, the three most commonly used are the Numerical Rating Scale, the Verbal Rating Scale, and the Visual Analog Scale, Dr. Jeffrey A. Stone said at the annual meeting of the Society of Neurointerventional Surgery.

"All of these scales have been shown to be statistically reliable and valid," said Dr. Stone, associate professor of neurointerventional surgery in the radiology department at the Mayo Clinic, Jacksonville, Fla. In his clinical experience, most patients prefer the Numerical Rating Scale (NRS) and the Verbal Rating Scale (VRS) because they are easy to use. "The other advantage is that these can be conducted by telephone or electronic diaries," he said.

The NRS is a familiar and commonly used 0-10 scale, where 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, and 7-10 = severe pain. "If patients tell you, ‘I’m a 5 out of 10,’ that can be difficult to gauge, particularly in the elderly," Dr. Stone said. "The VRS, a four-scale system ranging from no pain up to severe pain, is somewhat simpler and correlates well with the NRS."

With the Visual Analog Scale, patients are asked to make a vertical slash on a 100-mm line to denote their level of pain. "I use this scale a lot, but it can be cumbersome, particularly with follow-up," he said.

Factors to consider in the backdrop of pain intensity include rescue analgesics, which may be prescribed by other physicians for sleep or anxiety, or may be used to prevent pain from increased activity or to treat unrelated pain. "Another factor is concomitant pain treatments, such as acupuncture and chiropractic treatments," Dr. Stone said. "In addition, patients enrolled in the placebo group of a clinical trial are generally expected to have more pain medication use compared with those in an efficacious treatment group."

Other distinct components of pain include pain sensation and pain affect. Pain sensation "is the quality of the pain, such as burning, throbbing, or sharp pain versus dull pain," Dr. Stone said. "There are also temporal aspects to pain, such as variability of intensity over time; time to onset of meaningful pain relief; durability of pain relief; and the frequency, duration, and intensity of pain episodes. Pain affect is the mental distress caused by the pain."

Global pain assessments for pain sensation and pain affect include a modification of the McGill Pain Questionnaire (MPQ), known as the short-form MPQ, and the Brief Pain Inventory (BPI), which was adapted from the Wisconsin Brief Pain Questionnaire. The short-form MPQ contains 15 sensory and affective descriptors, while the BPI "does a much better job measuring the temporal aspect of pain and is often used in conjunction with the short-form MPQ," Dr. Stone said.

Two other core pain outcome domains are physical function and emotional function. Effective outcome measures for these domains include the Oswestry Disability Index (ODI), the Short Form-36 (SF-36), the Roland-Morris Disability Questionnaire (RMQ) and the Pain Disability Index (PDI).

The ODI, a 10-item questionnaire, "has been used in many pain trials," he said. "It looks at pain intensity but also other things such as lifting, the ability to walk, social life, sexual activity, and sleep cycle. It is a very accurate way to look at a patient’s global disability from pain."

He described the SF-36 as "a little bit more cumbersome for patients to complete" in measuring physical and emotional function. This tool provides an eight-scale profile of functional health and well-being scores, as well as a psychometric-based physical and mental health summary.

The 24-item RMQ consists of yes/no questions intended to measure self-perceived disability, while the 7-question PDI measures pain interference in physical and psychosocial role performance.

In a later interview, Dr. Stone said that the NRS, VRS, and VAS instruments can be used in hospitalized patients. Outcome measures such as the ODI and the RMQ "would not be very useful, as they ask many functional questions such as sex life [and] activity level, which would not be applicable to a hospitalized patient."

Dr. Stone said that he had no relevant financial disclosures to make.

SAN DIEGO – Of the many scales at a clinician’s disposal to measure acute pain, the three most commonly used are the Numerical Rating Scale, the Verbal Rating Scale, and the Visual Analog Scale, Dr. Jeffrey A. Stone said at the annual meeting of the Society of Neurointerventional Surgery.

"All of these scales have been shown to be statistically reliable and valid," said Dr. Stone, associate professor of neurointerventional surgery in the radiology department at the Mayo Clinic, Jacksonville, Fla. In his clinical experience, most patients prefer the Numerical Rating Scale (NRS) and the Verbal Rating Scale (VRS) because they are easy to use. "The other advantage is that these can be conducted by telephone or electronic diaries," he said.

The NRS is a familiar and commonly used 0-10 scale, where 0 = no pain, 1-3 = mild pain, 4-6 = moderate pain, and 7-10 = severe pain. "If patients tell you, ‘I’m a 5 out of 10,’ that can be difficult to gauge, particularly in the elderly," Dr. Stone said. "The VRS, a four-scale system ranging from no pain up to severe pain, is somewhat simpler and correlates well with the NRS."

With the Visual Analog Scale, patients are asked to make a vertical slash on a 100-mm line to denote their level of pain. "I use this scale a lot, but it can be cumbersome, particularly with follow-up," he said.

Factors to consider in the backdrop of pain intensity include rescue analgesics, which may be prescribed by other physicians for sleep or anxiety, or may be used to prevent pain from increased activity or to treat unrelated pain. "Another factor is concomitant pain treatments, such as acupuncture and chiropractic treatments," Dr. Stone said. "In addition, patients enrolled in the placebo group of a clinical trial are generally expected to have more pain medication use compared with those in an efficacious treatment group."

Other distinct components of pain include pain sensation and pain affect. Pain sensation "is the quality of the pain, such as burning, throbbing, or sharp pain versus dull pain," Dr. Stone said. "There are also temporal aspects to pain, such as variability of intensity over time; time to onset of meaningful pain relief; durability of pain relief; and the frequency, duration, and intensity of pain episodes. Pain affect is the mental distress caused by the pain."

Global pain assessments for pain sensation and pain affect include a modification of the McGill Pain Questionnaire (MPQ), known as the short-form MPQ, and the Brief Pain Inventory (BPI), which was adapted from the Wisconsin Brief Pain Questionnaire. The short-form MPQ contains 15 sensory and affective descriptors, while the BPI "does a much better job measuring the temporal aspect of pain and is often used in conjunction with the short-form MPQ," Dr. Stone said.

Two other core pain outcome domains are physical function and emotional function. Effective outcome measures for these domains include the Oswestry Disability Index (ODI), the Short Form-36 (SF-36), the Roland-Morris Disability Questionnaire (RMQ) and the Pain Disability Index (PDI).

The ODI, a 10-item questionnaire, "has been used in many pain trials," he said. "It looks at pain intensity but also other things such as lifting, the ability to walk, social life, sexual activity, and sleep cycle. It is a very accurate way to look at a patient’s global disability from pain."

He described the SF-36 as "a little bit more cumbersome for patients to complete" in measuring physical and emotional function. This tool provides an eight-scale profile of functional health and well-being scores, as well as a psychometric-based physical and mental health summary.

The 24-item RMQ consists of yes/no questions intended to measure self-perceived disability, while the 7-question PDI measures pain interference in physical and psychosocial role performance.

In a later interview, Dr. Stone said that the NRS, VRS, and VAS instruments can be used in hospitalized patients. Outcome measures such as the ODI and the RMQ "would not be very useful, as they ask many functional questions such as sex life [and] activity level, which would not be applicable to a hospitalized patient."

Dr. Stone said that he had no relevant financial disclosures to make.

AMSTERDAM  – Ask a hematologist about the most serious quality of life issues for patients with multiple myeloma, and neuropathy typically tops the list. But fatigue, malaise, or muscle weakness was more often concerning to patients who answered a survey on treatment-related side effects.

Cancer patients and their physicians differ to a large extent in their perceptions of a treatment’s impact on quality of life, according to Eric Low, the founder and chief executive of Myeloma UK. Even caregivers with a clear view of day-to-day realities may not see the patients’ point of view.

Although the patients’ caregivers "will often have a more accurate insight into how the cancer is affecting patients than the patients themselves, patients put more emphasis on quality than on longevity of life," he observed, citing data from the United Kingdom and from Europe, with myeloma patients specifically.

Contradictions in how patients and practitioners perceive quality of life was a recurrent theme in talks by patient advocates at the recent annual congress of the European Hematology Association. They described efforts to give patients a stronger voice through Internet-based questionnaires, physician guidelines, and tools for quality of life (QoL) assessment.

"There is such a large difference in perception of quality of life and what doctors think of quality of life in practice of a therapy and symptoms of disease, and what patients perceive about their impact on quality of life and symptoms," said Jan Geissler, a cofounder of the CML [Chronic Myeloid Leukemia] Advocates Network and director of the EUPATI (European Patients’ Academy on Therapeutic Innovation).

For patients on therapy, the need "is not only survival, but includes a lot of factors including quality of life – including, let’s say, how to cope with the disease, psychological factors," added Mr. Geissler, a CML survivor.

Survey Pinpoints Discrepancies

In 2009, Myeloma Euronet – which recently changed its name to Myeloma Patients Europe – conducted a survey to look at the effects of treatment side effects and unmet patient needs in patients with multiple myeloma. The aim was to look at, and compare, the opinions of those affected by the disease, including family members and general caregivers, vs. those of the medical profession.

A total of 314 health care professionals – among them 217 hematologists, 15 medical oncologists, 8 hematologist-oncologists, 68 nurses, and 5 other professionals – from 43 countries took part.

Participants also included 173 patients with multiple myeloma from 17 countries, and 85 relatives and 2 caregivers participating on behalf of myeloma patients from 13 countries. The largest patient contingent came from Poland.

The findings were enlightening, Mr. Low said. Patients and health care providers viewed the potential negative impact of several treatment-related side effects on overall well-being very differently.

Among physicians and nurses (83% and 77%, respectively), neuropathy was most often cited as having a negative impact on a patients’ well-being.

This was followed by a broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia, which was cited more often by nurses (72%) than by physicians (60%).

For physicians, infection had the third most negative impact. It was cited by (56%), followed by pain (48%) and thrombotic events (47%). A majority (62%) of nurses put nausea and vomiting in the No. 3 spot, however, followed by pain (57%). Infections and effects on the stomach and/or colon were each cited by 47% of nurses.

Among patients, relatives, and caregivers, the treatment side effect most often cited as compromising daily life fell into the broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia. This was cited by 73% of patients and 70% of their relatives and caregivers.

Neuropathy ranked second in negative impact for patients (54%) but was cited less often (45%) by relatives and caregivers, who put effects on the stomach and/or colon in second place (55%). Whereas decreased body function followed as No. 3 in negative impact among patients (53%), hair loss was cited by 52% of relatives and caregivers.

There were also several treatment-related side effects that patients did not report to their doctor, perhaps because they felt uncomfortable to do so. These included sexual problems, diarrhea, constipation, gastrointestinal upsets, and psychological issues, among others.

"Patients often put on a brave face, don’t want to let the side down, and associate [having] a positive outlook with therapeutic benefit," observed Mr. Low.

Moreover, balancing efficacy against side effects is "not what drives the patient all the time," he said. What patients want from treatment is very individual; although some patients may want greater choice or involvement in making decisions about their care, others may not. Some may prefer convenience or fewer side effects; others may want maximum disease control and a long, durable remission.

"It’s important that doctors tweak out what the objectives are for each individual patient and try to facilitate these in terms of how they are managed, and what treatments options are available," Mr. Low said. Quality of life should be considered as much as clinical outcomes, he suggested.

RareConnect Gathers Patient-Reported Information

An initiative called RareConnect could help provide important information about the effects of treatment from the patient perspective. Run by the EURODIS (European Organization for Rare Diseases), and by the U.S.-based NORD (National Organization for Rare Disorders), RareConnect is a social network of rare-disease communities that offers users the opportunity to assess patient-reported quality of life via a series of Internet-based questionnaires.

"What we are trying to do is bring a certain sense of structure now to the way patients can report on outcomes, essentially," said Denis Costello, who is leading the RareConnect project on behalf of EURODIS.

A pilot project is underway in patients with myeloma, he added in an interview. The Internet-based tool involves a series of interactive questionnaires that patients answer at a minimum of once a week. The collected information will include when patients were diagnosed, what treatments they have used, and their sliding-scale ratings of any side effects they have experienced.

RareConnect also allows patients to see how they compare with the rest of the community, and they can discuss their condition with others who are in a similar situation.

To develop a patient-friendly tool with the right level of lightness has been challenging because physicians want it to follow the lines of the quality of life scales and currently available instruments, Mr. Costello said. Physicians "want to get statistically significant data, but patients, we know, are not going to fill in those kinds of questionnaires."

Ultimately, "we want to provide a tool to patients to help them better self-manage their own outcomes in conjunction with their [health care professional], because we feel that this tool can help the patient, and bring a new dynamism between patient and doctor," he explained.

"It’s about discussion, really," Mr. Costello added, noting that the tool could help patients be more aware of their treatment and how it may affect them. In myeloma, for example, it could help prevent patients’ stopping treatment too early and later suffering a relapse.

"We really want to empower patients to see that [perhaps] you need to stay on the treatment a bit longer, and sometimes you need to fight," he suggested. RareConnect and other similar initiatives could provide the starting evidence that patients need to discuss such issues with their doctor.

Measuring Quality of Life

The European Hematology Association’s Scientific Working Group on Quality of Life and Symptoms has just published guidelines on how to assess quality of life in patients with hematologic disorders. Aimed at the practicing hematologist, these guidelines cover hematological malignancies, as well as other blood conditions.

"As physicians, as researchers, we understand that we do have new treatment modalities; we are able to provide good quality of care, but it very important to have the patient perspective to know if we are doing everything in the right way," said Tatyana Ionova, Ph.D., professor of the Postgraduate Education Institute at the National Medical Surgical Center Northwestern Branch in St. Petersburg, Russian Federation.

"Sometimes we may have information about the success or benefit or risks of treatment only from the patient perspective. That is why we try to develop the instruments, [which are] standardized measures that are able to ask the patients about their physical, social, psychological well-being, about [their] symptoms," Dr. Ionova said.

The EHA guidelines on "Patient-Reported Outcomes in Hematology" recognize that there are differences between hematologic diseases in terms of the quality of life assessments that can be used, "because bone marrow transplantation is very different from ITP [immune thrombocytopenic purpura," Dr. Ionova noted.

So how should hematologists measure quality of life? "First, read the guidelines," she suggested. "Then, have some very simple training about the questionnaires and how to use them."

These questionnaires shouldn’t take very long to be completed by or with the patient, she added. The important thing is that quality of life is considered.

The Myeloma Euronet survey was made possible through an unrestricted grant from Ortho Biotech. All authors reported no relevant disclosures other than working for their respective organizations.

AMSTERDAM  – Ask a hematologist about the most serious quality of life issues for patients with multiple myeloma, and neuropathy typically tops the list. But fatigue, malaise, or muscle weakness was more often concerning to patients who answered a survey on treatment-related side effects.

Cancer patients and their physicians differ to a large extent in their perceptions of a treatment’s impact on quality of life, according to Eric Low, the founder and chief executive of Myeloma UK. Even caregivers with a clear view of day-to-day realities may not see the patients’ point of view.

Although the patients’ caregivers "will often have a more accurate insight into how the cancer is affecting patients than the patients themselves, patients put more emphasis on quality than on longevity of life," he observed, citing data from the United Kingdom and from Europe, with myeloma patients specifically.

Contradictions in how patients and practitioners perceive quality of life was a recurrent theme in talks by patient advocates at the recent annual congress of the European Hematology Association. They described efforts to give patients a stronger voice through Internet-based questionnaires, physician guidelines, and tools for quality of life (QoL) assessment.

"There is such a large difference in perception of quality of life and what doctors think of quality of life in practice of a therapy and symptoms of disease, and what patients perceive about their impact on quality of life and symptoms," said Jan Geissler, a cofounder of the CML [Chronic Myeloid Leukemia] Advocates Network and director of the EUPATI (European Patients’ Academy on Therapeutic Innovation).

For patients on therapy, the need "is not only survival, but includes a lot of factors including quality of life – including, let’s say, how to cope with the disease, psychological factors," added Mr. Geissler, a CML survivor.

Survey Pinpoints Discrepancies

In 2009, Myeloma Euronet – which recently changed its name to Myeloma Patients Europe – conducted a survey to look at the effects of treatment side effects and unmet patient needs in patients with multiple myeloma. The aim was to look at, and compare, the opinions of those affected by the disease, including family members and general caregivers, vs. those of the medical profession.

A total of 314 health care professionals – among them 217 hematologists, 15 medical oncologists, 8 hematologist-oncologists, 68 nurses, and 5 other professionals – from 43 countries took part.

Participants also included 173 patients with multiple myeloma from 17 countries, and 85 relatives and 2 caregivers participating on behalf of myeloma patients from 13 countries. The largest patient contingent came from Poland.

The findings were enlightening, Mr. Low said. Patients and health care providers viewed the potential negative impact of several treatment-related side effects on overall well-being very differently.

Among physicians and nurses (83% and 77%, respectively), neuropathy was most often cited as having a negative impact on a patients’ well-being.

This was followed by a broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia, which was cited more often by nurses (72%) than by physicians (60%).

For physicians, infection had the third most negative impact. It was cited by (56%), followed by pain (48%) and thrombotic events (47%). A majority (62%) of nurses put nausea and vomiting in the No. 3 spot, however, followed by pain (57%). Infections and effects on the stomach and/or colon were each cited by 47% of nurses.

Among patients, relatives, and caregivers, the treatment side effect most often cited as compromising daily life fell into the broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia. This was cited by 73% of patients and 70% of their relatives and caregivers.

Neuropathy ranked second in negative impact for patients (54%) but was cited less often (45%) by relatives and caregivers, who put effects on the stomach and/or colon in second place (55%). Whereas decreased body function followed as No. 3 in negative impact among patients (53%), hair loss was cited by 52% of relatives and caregivers.

There were also several treatment-related side effects that patients did not report to their doctor, perhaps because they felt uncomfortable to do so. These included sexual problems, diarrhea, constipation, gastrointestinal upsets, and psychological issues, among others.

"Patients often put on a brave face, don’t want to let the side down, and associate [having] a positive outlook with therapeutic benefit," observed Mr. Low.

Moreover, balancing efficacy against side effects is "not what drives the patient all the time," he said. What patients want from treatment is very individual; although some patients may want greater choice or involvement in making decisions about their care, others may not. Some may prefer convenience or fewer side effects; others may want maximum disease control and a long, durable remission.

"It’s important that doctors tweak out what the objectives are for each individual patient and try to facilitate these in terms of how they are managed, and what treatments options are available," Mr. Low said. Quality of life should be considered as much as clinical outcomes, he suggested.

RareConnect Gathers Patient-Reported Information

An initiative called RareConnect could help provide important information about the effects of treatment from the patient perspective. Run by the EURODIS (European Organization for Rare Diseases), and by the U.S.-based NORD (National Organization for Rare Disorders), RareConnect is a social network of rare-disease communities that offers users the opportunity to assess patient-reported quality of life via a series of Internet-based questionnaires.

"What we are trying to do is bring a certain sense of structure now to the way patients can report on outcomes, essentially," said Denis Costello, who is leading the RareConnect project on behalf of EURODIS.

A pilot project is underway in patients with myeloma, he added in an interview. The Internet-based tool involves a series of interactive questionnaires that patients answer at a minimum of once a week. The collected information will include when patients were diagnosed, what treatments they have used, and their sliding-scale ratings of any side effects they have experienced.

RareConnect also allows patients to see how they compare with the rest of the community, and they can discuss their condition with others who are in a similar situation.

To develop a patient-friendly tool with the right level of lightness has been challenging because physicians want it to follow the lines of the quality of life scales and currently available instruments, Mr. Costello said. Physicians "want to get statistically significant data, but patients, we know, are not going to fill in those kinds of questionnaires."

Ultimately, "we want to provide a tool to patients to help them better self-manage their own outcomes in conjunction with their [health care professional], because we feel that this tool can help the patient, and bring a new dynamism between patient and doctor," he explained.

"It’s about discussion, really," Mr. Costello added, noting that the tool could help patients be more aware of their treatment and how it may affect them. In myeloma, for example, it could help prevent patients’ stopping treatment too early and later suffering a relapse.

"We really want to empower patients to see that [perhaps] you need to stay on the treatment a bit longer, and sometimes you need to fight," he suggested. RareConnect and other similar initiatives could provide the starting evidence that patients need to discuss such issues with their doctor.

Measuring Quality of Life

The European Hematology Association’s Scientific Working Group on Quality of Life and Symptoms has just published guidelines on how to assess quality of life in patients with hematologic disorders. Aimed at the practicing hematologist, these guidelines cover hematological malignancies, as well as other blood conditions.

"As physicians, as researchers, we understand that we do have new treatment modalities; we are able to provide good quality of care, but it very important to have the patient perspective to know if we are doing everything in the right way," said Tatyana Ionova, Ph.D., professor of the Postgraduate Education Institute at the National Medical Surgical Center Northwestern Branch in St. Petersburg, Russian Federation.

"Sometimes we may have information about the success or benefit or risks of treatment only from the patient perspective. That is why we try to develop the instruments, [which are] standardized measures that are able to ask the patients about their physical, social, psychological well-being, about [their] symptoms," Dr. Ionova said.

The EHA guidelines on "Patient-Reported Outcomes in Hematology" recognize that there are differences between hematologic diseases in terms of the quality of life assessments that can be used, "because bone marrow transplantation is very different from ITP [immune thrombocytopenic purpura," Dr. Ionova noted.

So how should hematologists measure quality of life? "First, read the guidelines," she suggested. "Then, have some very simple training about the questionnaires and how to use them."

These questionnaires shouldn’t take very long to be completed by or with the patient, she added. The important thing is that quality of life is considered.

The Myeloma Euronet survey was made possible through an unrestricted grant from Ortho Biotech. All authors reported no relevant disclosures other than working for their respective organizations.

AMSTERDAM  – Ask a hematologist about the most serious quality of life issues for patients with multiple myeloma, and neuropathy typically tops the list. But fatigue, malaise, or muscle weakness was more often concerning to patients who answered a survey on treatment-related side effects.

Cancer patients and their physicians differ to a large extent in their perceptions of a treatment’s impact on quality of life, according to Eric Low, the founder and chief executive of Myeloma UK. Even caregivers with a clear view of day-to-day realities may not see the patients’ point of view.

Although the patients’ caregivers "will often have a more accurate insight into how the cancer is affecting patients than the patients themselves, patients put more emphasis on quality than on longevity of life," he observed, citing data from the United Kingdom and from Europe, with myeloma patients specifically.

Contradictions in how patients and practitioners perceive quality of life was a recurrent theme in talks by patient advocates at the recent annual congress of the European Hematology Association. They described efforts to give patients a stronger voice through Internet-based questionnaires, physician guidelines, and tools for quality of life (QoL) assessment.

"There is such a large difference in perception of quality of life and what doctors think of quality of life in practice of a therapy and symptoms of disease, and what patients perceive about their impact on quality of life and symptoms," said Jan Geissler, a cofounder of the CML [Chronic Myeloid Leukemia] Advocates Network and director of the EUPATI (European Patients’ Academy on Therapeutic Innovation).

For patients on therapy, the need "is not only survival, but includes a lot of factors including quality of life – including, let’s say, how to cope with the disease, psychological factors," added Mr. Geissler, a CML survivor.

Survey Pinpoints Discrepancies

In 2009, Myeloma Euronet – which recently changed its name to Myeloma Patients Europe – conducted a survey to look at the effects of treatment side effects and unmet patient needs in patients with multiple myeloma. The aim was to look at, and compare, the opinions of those affected by the disease, including family members and general caregivers, vs. those of the medical profession.

A total of 314 health care professionals – among them 217 hematologists, 15 medical oncologists, 8 hematologist-oncologists, 68 nurses, and 5 other professionals – from 43 countries took part.

Participants also included 173 patients with multiple myeloma from 17 countries, and 85 relatives and 2 caregivers participating on behalf of myeloma patients from 13 countries. The largest patient contingent came from Poland.

The findings were enlightening, Mr. Low said. Patients and health care providers viewed the potential negative impact of several treatment-related side effects on overall well-being very differently.

Among physicians and nurses (83% and 77%, respectively), neuropathy was most often cited as having a negative impact on a patients’ well-being.

This was followed by a broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia, which was cited more often by nurses (72%) than by physicians (60%).

For physicians, infection had the third most negative impact. It was cited by (56%), followed by pain (48%) and thrombotic events (47%). A majority (62%) of nurses put nausea and vomiting in the No. 3 spot, however, followed by pain (57%). Infections and effects on the stomach and/or colon were each cited by 47% of nurses.

Among patients, relatives, and caregivers, the treatment side effect most often cited as compromising daily life fell into the broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia. This was cited by 73% of patients and 70% of their relatives and caregivers.

Neuropathy ranked second in negative impact for patients (54%) but was cited less often (45%) by relatives and caregivers, who put effects on the stomach and/or colon in second place (55%). Whereas decreased body function followed as No. 3 in negative impact among patients (53%), hair loss was cited by 52% of relatives and caregivers.

There were also several treatment-related side effects that patients did not report to their doctor, perhaps because they felt uncomfortable to do so. These included sexual problems, diarrhea, constipation, gastrointestinal upsets, and psychological issues, among others.

"Patients often put on a brave face, don’t want to let the side down, and associate [having] a positive outlook with therapeutic benefit," observed Mr. Low.

Moreover, balancing efficacy against side effects is "not what drives the patient all the time," he said. What patients want from treatment is very individual; although some patients may want greater choice or involvement in making decisions about their care, others may not. Some may prefer convenience or fewer side effects; others may want maximum disease control and a long, durable remission.

"It’s important that doctors tweak out what the objectives are for each individual patient and try to facilitate these in terms of how they are managed, and what treatments options are available," Mr. Low said. Quality of life should be considered as much as clinical outcomes, he suggested.

RareConnect Gathers Patient-Reported Information

An initiative called RareConnect could help provide important information about the effects of treatment from the patient perspective. Run by the EURODIS (European Organization for Rare Diseases), and by the U.S.-based NORD (National Organization for Rare Disorders), RareConnect is a social network of rare-disease communities that offers users the opportunity to assess patient-reported quality of life via a series of Internet-based questionnaires.

"What we are trying to do is bring a certain sense of structure now to the way patients can report on outcomes, essentially," said Denis Costello, who is leading the RareConnect project on behalf of EURODIS.

A pilot project is underway in patients with myeloma, he added in an interview. The Internet-based tool involves a series of interactive questionnaires that patients answer at a minimum of once a week. The collected information will include when patients were diagnosed, what treatments they have used, and their sliding-scale ratings of any side effects they have experienced.

RareConnect also allows patients to see how they compare with the rest of the community, and they can discuss their condition with others who are in a similar situation.

To develop a patient-friendly tool with the right level of lightness has been challenging because physicians want it to follow the lines of the quality of life scales and currently available instruments, Mr. Costello said. Physicians "want to get statistically significant data, but patients, we know, are not going to fill in those kinds of questionnaires."

Ultimately, "we want to provide a tool to patients to help them better self-manage their own outcomes in conjunction with their [health care professional], because we feel that this tool can help the patient, and bring a new dynamism between patient and doctor," he explained.

"It’s about discussion, really," Mr. Costello added, noting that the tool could help patients be more aware of their treatment and how it may affect them. In myeloma, for example, it could help prevent patients’ stopping treatment too early and later suffering a relapse.

"We really want to empower patients to see that [perhaps] you need to stay on the treatment a bit longer, and sometimes you need to fight," he suggested. RareConnect and other similar initiatives could provide the starting evidence that patients need to discuss such issues with their doctor.

Measuring Quality of Life

The European Hematology Association’s Scientific Working Group on Quality of Life and Symptoms has just published guidelines on how to assess quality of life in patients with hematologic disorders. Aimed at the practicing hematologist, these guidelines cover hematological malignancies, as well as other blood conditions.

"As physicians, as researchers, we understand that we do have new treatment modalities; we are able to provide good quality of care, but it very important to have the patient perspective to know if we are doing everything in the right way," said Tatyana Ionova, Ph.D., professor of the Postgraduate Education Institute at the National Medical Surgical Center Northwestern Branch in St. Petersburg, Russian Federation.

"Sometimes we may have information about the success or benefit or risks of treatment only from the patient perspective. That is why we try to develop the instruments, [which are] standardized measures that are able to ask the patients about their physical, social, psychological well-being, about [their] symptoms," Dr. Ionova said.

The EHA guidelines on "Patient-Reported Outcomes in Hematology" recognize that there are differences between hematologic diseases in terms of the quality of life assessments that can be used, "because bone marrow transplantation is very different from ITP [immune thrombocytopenic purpura," Dr. Ionova noted.

So how should hematologists measure quality of life? "First, read the guidelines," she suggested. "Then, have some very simple training about the questionnaires and how to use them."

These questionnaires shouldn’t take very long to be completed by or with the patient, she added. The important thing is that quality of life is considered.

The Myeloma Euronet survey was made possible through an unrestricted grant from Ortho Biotech. All authors reported no relevant disclosures other than working for their respective organizations.

Depression does more than strike at the heart; it can compromise survival for patients with metastatic kidney cancer.

Researchers from the University of Texas M.D. Anderson Cancer Center in Houston found that patients with higher levels of cortisol – a stress hormone linked with depression – died significantly sooner than those with lower cortisol levels (hazard ratio, 1.9; P = .002).

The prospective study accrued 217 patients with newly diagnosed metastatic renal cell carcinoma (RCC) from 2000 to 2007. Participants completed psychosocial questionnaires; saliva and blood samples also were collected.

Nearly a quarter (23%) of the population had a score of 16 or greater on the CES-D (Centers for Epidemiologic StudiesDepression) scale, which met criteria for depressive symptoms and was also associated with shorter survival, compared with lower scores (HR, 1.5; P = .05).

Genomic analysis suggested a biological underpinning for the observed link, reported Lorenzo Cohen, Ph.D., a professor in M.D. Anderson’s departments of general oncology and behavioral science and director of the integrative medicine program, and his coauthors. Patients with high cortisol levels had marked up-regulation of proinflammatory genes.

"Collectively, the present data suggest that the association between RCC patient psychological condition and survival time may stem from systemic dysregulation of inflammatory biology resulting from blunted cortisol rhythmicity and subsequent de-repression of pro-inflammatory signaling pathways within the tumor microenvironment that subsequently contribute to disease progression and metastasis," wrote the investigators. (PLoS ONE 2012 Aug. 1 [doi:10.1371/journal.pone.0042324]).

Grants from the Dana Foundation, the Mary and David Wolff Family Foundation, the U.S. Department of Health and Human Services, the National Institutes of Health, and the M.D. Anderson Cancer Center supported the research.

Depression does more than strike at the heart; it can compromise survival for patients with metastatic kidney cancer.

Researchers from the University of Texas M.D. Anderson Cancer Center in Houston found that patients with higher levels of cortisol – a stress hormone linked with depression – died significantly sooner than those with lower cortisol levels (hazard ratio, 1.9; P = .002).

The prospective study accrued 217 patients with newly diagnosed metastatic renal cell carcinoma (RCC) from 2000 to 2007. Participants completed psychosocial questionnaires; saliva and blood samples also were collected.

Nearly a quarter (23%) of the population had a score of 16 or greater on the CES-D (Centers for Epidemiologic StudiesDepression) scale, which met criteria for depressive symptoms and was also associated with shorter survival, compared with lower scores (HR, 1.5; P = .05).

Genomic analysis suggested a biological underpinning for the observed link, reported Lorenzo Cohen, Ph.D., a professor in M.D. Anderson’s departments of general oncology and behavioral science and director of the integrative medicine program, and his coauthors. Patients with high cortisol levels had marked up-regulation of proinflammatory genes.

"Collectively, the present data suggest that the association between RCC patient psychological condition and survival time may stem from systemic dysregulation of inflammatory biology resulting from blunted cortisol rhythmicity and subsequent de-repression of pro-inflammatory signaling pathways within the tumor microenvironment that subsequently contribute to disease progression and metastasis," wrote the investigators. (PLoS ONE 2012 Aug. 1 [doi:10.1371/journal.pone.0042324]).

Grants from the Dana Foundation, the Mary and David Wolff Family Foundation, the U.S. Department of Health and Human Services, the National Institutes of Health, and the M.D. Anderson Cancer Center supported the research.

Depression does more than strike at the heart; it can compromise survival for patients with metastatic kidney cancer.

Researchers from the University of Texas M.D. Anderson Cancer Center in Houston found that patients with higher levels of cortisol – a stress hormone linked with depression – died significantly sooner than those with lower cortisol levels (hazard ratio, 1.9; P = .002).

The prospective study accrued 217 patients with newly diagnosed metastatic renal cell carcinoma (RCC) from 2000 to 2007. Participants completed psychosocial questionnaires; saliva and blood samples also were collected.

Nearly a quarter (23%) of the population had a score of 16 or greater on the CES-D (Centers for Epidemiologic StudiesDepression) scale, which met criteria for depressive symptoms and was also associated with shorter survival, compared with lower scores (HR, 1.5; P = .05).

Genomic analysis suggested a biological underpinning for the observed link, reported Lorenzo Cohen, Ph.D., a professor in M.D. Anderson’s departments of general oncology and behavioral science and director of the integrative medicine program, and his coauthors. Patients with high cortisol levels had marked up-regulation of proinflammatory genes.

"Collectively, the present data suggest that the association between RCC patient psychological condition and survival time may stem from systemic dysregulation of inflammatory biology resulting from blunted cortisol rhythmicity and subsequent de-repression of pro-inflammatory signaling pathways within the tumor microenvironment that subsequently contribute to disease progression and metastasis," wrote the investigators. (PLoS ONE 2012 Aug. 1 [doi:10.1371/journal.pone.0042324]).

Grants from the Dana Foundation, the Mary and David Wolff Family Foundation, the U.S. Department of Health and Human Services, the National Institutes of Health, and the M.D. Anderson Cancer Center supported the research.

ORLANDO – Oral isotretinoin holds potential as a bridge therapy for cancer patients who develop severe rashes during treatment, according to Dr. Milan J. Anadkat.

Dermatologists can play an integral role here. "Most oncologists see these patients first, and most oncologists are not enrolled in the iPledge program," said Dr. Anadkat of the division of dermatology at Washington University in St. Louis.

He noted that all treatment options are off label because there are no Food and Drug Administration–approved agents to treat chemotherapy-related cutaneous toxicities.

Getting patients through rashes that occur within a week or two of beginning targeted chemotherapy is important, as patients who develop the greatest reactions tend to have cancers that respond best to treatment, said Dr. Anadkat at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery. For this reason, the management of these patients is more complicated than simple drug cessation.

"The problem with just taking them off the drug is that they have cancer. Ultimately, the big goal here is treating the cancer, not avoiding the rash," he said.

Tetracycline or doxycycline can also reduce the severity of the rash, but the timing of administration is important. Better outcomes are associated with prophylaxis that is timed with the initiation of EGFR (epidermal growth factor receptor) inhibitors (Cancer 2008;113:847-53). "Waiting for the rash to appear is not the time to give it. It makes a difference if you give at day 0, not in terms of incidence but in the severity of the rash," he said.

Educate patients that the rash typically appears in an estimated 60%-90% of people within 8-10 days of EGFR inhibitor initiation, with a peak presentation at 2-4 weeks. "Bridging them through with something as effective as isotretinoin is useful," said Dr. Anadkat.

The rash generally appears on the face and upper trunk, but be careful not to confuse the presentation with a photo-exposure phenomenon.

Although some oncologists will describe the skin eruptions as "acnelike," histology will show mixed inflammatory infiltrate and follicular rupture. For this reason, "topical acne medications do very little," Dr. Anadkat said. Also, rule out infection, except when patients present with pustules on their arms, legs, or other non–EGFR receptor areas.

EGFR inhibitors can cause inflammatory alopecia, eyelash trichomegaly, and periungual and nail alterations.

About one in six patients will develop periungual or nail abnormalities, typically on their first finger or toe. These effects can be painful, Dr. Anadkat said. Culture is mandatory to rule out superinfection.

Again, the approach is to get patients through the adverse events with petroleum jelly, high-dose topical steroids, or oral tetracyclines. "Tumor markers are going down; [oncologists] are not going to want to stop chemotherapy for a painful thumb or toe," he said. "I recommend antimicrobial soaks with bleach or vinegar to prevent paronychia superinfection."

Dry, itchy skin is another concern with long-term EGFR inhibitor treatment. Histology shows "stark differences" in the stratum corneum. "This is the No. 1 side effect for patients on long-term EGFR – 3 months or longer; [it is] not a grade 3 or higher toxicity, but it is annoying."

Investigators compared oral minocycline and topical tazarotene prophylaxis in a study of 48 patients with cetuximab associated rash (J. Clin. Oncol. 2007:25:5390-6). Although oral minocycline was associated with reduced lesion counts, topical tazarotene yielded no significant benefit. "Again, this is not acne," Dr. Anadkat said.

He disclosed being a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, and ImClone regarding strategies for managing skin toxicities from chemotherapy. He has never prescribed chemotherapy agents.

ORLANDO – Oral isotretinoin holds potential as a bridge therapy for cancer patients who develop severe rashes during treatment, according to Dr. Milan J. Anadkat.

Dermatologists can play an integral role here. "Most oncologists see these patients first, and most oncologists are not enrolled in the iPledge program," said Dr. Anadkat of the division of dermatology at Washington University in St. Louis.

He noted that all treatment options are off label because there are no Food and Drug Administration–approved agents to treat chemotherapy-related cutaneous toxicities.

Getting patients through rashes that occur within a week or two of beginning targeted chemotherapy is important, as patients who develop the greatest reactions tend to have cancers that respond best to treatment, said Dr. Anadkat at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery. For this reason, the management of these patients is more complicated than simple drug cessation.

"The problem with just taking them off the drug is that they have cancer. Ultimately, the big goal here is treating the cancer, not avoiding the rash," he said.

Tetracycline or doxycycline can also reduce the severity of the rash, but the timing of administration is important. Better outcomes are associated with prophylaxis that is timed with the initiation of EGFR (epidermal growth factor receptor) inhibitors (Cancer 2008;113:847-53). "Waiting for the rash to appear is not the time to give it. It makes a difference if you give at day 0, not in terms of incidence but in the severity of the rash," he said.

Educate patients that the rash typically appears in an estimated 60%-90% of people within 8-10 days of EGFR inhibitor initiation, with a peak presentation at 2-4 weeks. "Bridging them through with something as effective as isotretinoin is useful," said Dr. Anadkat.

The rash generally appears on the face and upper trunk, but be careful not to confuse the presentation with a photo-exposure phenomenon.

Although some oncologists will describe the skin eruptions as "acnelike," histology will show mixed inflammatory infiltrate and follicular rupture. For this reason, "topical acne medications do very little," Dr. Anadkat said. Also, rule out infection, except when patients present with pustules on their arms, legs, or other non–EGFR receptor areas.

EGFR inhibitors can cause inflammatory alopecia, eyelash trichomegaly, and periungual and nail alterations.

About one in six patients will develop periungual or nail abnormalities, typically on their first finger or toe. These effects can be painful, Dr. Anadkat said. Culture is mandatory to rule out superinfection.

Again, the approach is to get patients through the adverse events with petroleum jelly, high-dose topical steroids, or oral tetracyclines. "Tumor markers are going down; [oncologists] are not going to want to stop chemotherapy for a painful thumb or toe," he said. "I recommend antimicrobial soaks with bleach or vinegar to prevent paronychia superinfection."

Dry, itchy skin is another concern with long-term EGFR inhibitor treatment. Histology shows "stark differences" in the stratum corneum. "This is the No. 1 side effect for patients on long-term EGFR – 3 months or longer; [it is] not a grade 3 or higher toxicity, but it is annoying."

Investigators compared oral minocycline and topical tazarotene prophylaxis in a study of 48 patients with cetuximab associated rash (J. Clin. Oncol. 2007:25:5390-6). Although oral minocycline was associated with reduced lesion counts, topical tazarotene yielded no significant benefit. "Again, this is not acne," Dr. Anadkat said.

He disclosed being a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, and ImClone regarding strategies for managing skin toxicities from chemotherapy. He has never prescribed chemotherapy agents.

ORLANDO – Oral isotretinoin holds potential as a bridge therapy for cancer patients who develop severe rashes during treatment, according to Dr. Milan J. Anadkat.

Dermatologists can play an integral role here. "Most oncologists see these patients first, and most oncologists are not enrolled in the iPledge program," said Dr. Anadkat of the division of dermatology at Washington University in St. Louis.

He noted that all treatment options are off label because there are no Food and Drug Administration–approved agents to treat chemotherapy-related cutaneous toxicities.

Getting patients through rashes that occur within a week or two of beginning targeted chemotherapy is important, as patients who develop the greatest reactions tend to have cancers that respond best to treatment, said Dr. Anadkat at the annual meeting of the Florida Society of Dermatology and Dermatologic Surgery. For this reason, the management of these patients is more complicated than simple drug cessation.

"The problem with just taking them off the drug is that they have cancer. Ultimately, the big goal here is treating the cancer, not avoiding the rash," he said.

Tetracycline or doxycycline can also reduce the severity of the rash, but the timing of administration is important. Better outcomes are associated with prophylaxis that is timed with the initiation of EGFR (epidermal growth factor receptor) inhibitors (Cancer 2008;113:847-53). "Waiting for the rash to appear is not the time to give it. It makes a difference if you give at day 0, not in terms of incidence but in the severity of the rash," he said.

Educate patients that the rash typically appears in an estimated 60%-90% of people within 8-10 days of EGFR inhibitor initiation, with a peak presentation at 2-4 weeks. "Bridging them through with something as effective as isotretinoin is useful," said Dr. Anadkat.

The rash generally appears on the face and upper trunk, but be careful not to confuse the presentation with a photo-exposure phenomenon.

Although some oncologists will describe the skin eruptions as "acnelike," histology will show mixed inflammatory infiltrate and follicular rupture. For this reason, "topical acne medications do very little," Dr. Anadkat said. Also, rule out infection, except when patients present with pustules on their arms, legs, or other non–EGFR receptor areas.

EGFR inhibitors can cause inflammatory alopecia, eyelash trichomegaly, and periungual and nail alterations.

About one in six patients will develop periungual or nail abnormalities, typically on their first finger or toe. These effects can be painful, Dr. Anadkat said. Culture is mandatory to rule out superinfection.

Again, the approach is to get patients through the adverse events with petroleum jelly, high-dose topical steroids, or oral tetracyclines. "Tumor markers are going down; [oncologists] are not going to want to stop chemotherapy for a painful thumb or toe," he said. "I recommend antimicrobial soaks with bleach or vinegar to prevent paronychia superinfection."

Dry, itchy skin is another concern with long-term EGFR inhibitor treatment. Histology shows "stark differences" in the stratum corneum. "This is the No. 1 side effect for patients on long-term EGFR – 3 months or longer; [it is] not a grade 3 or higher toxicity, but it is annoying."

Investigators compared oral minocycline and topical tazarotene prophylaxis in a study of 48 patients with cetuximab associated rash (J. Clin. Oncol. 2007:25:5390-6). Although oral minocycline was associated with reduced lesion counts, topical tazarotene yielded no significant benefit. "Again, this is not acne," Dr. Anadkat said.

He disclosed being a consultant or speaker for AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, and ImClone regarding strategies for managing skin toxicities from chemotherapy. He has never prescribed chemotherapy agents.

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

Dr. Medvedev said that she had no disclosures.

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

Dr. Medvedev said that she had no disclosures.

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

Dr. Medvedev said that she had no disclosures.

CHICAGO – Long-term therapy with monthly zoledronic acid provides sustained survival benefits over daily oral bisphosphonates in multiple myeloma, with no evidence of a cumulative increase in the risk of osteonecrosis of the jaw.

After a median follow-up of 5.8 years in the MRC (U.K. Medical Research Council) Myeloma IX trial, zoledronic acid (Zometa) significantly improved the primary end points of progression-free survival (19 months vs. 18 months; hazard ratio, 0.88; P = .01) and overall survival (51 months vs. 46 months; HR, 0.88; P = .03) compared with oral clodronate. Patients in both arms of the trial received first-line intensive or nonintensive chemotherapy.

The overall cumulative incidence of osteonecrosis of the jaw (ONJ) was low, at 3.7% for zoledronic acid and 0.5% for clodronate (P less than .0001), Dr. Gareth J. Morgan reported at the annual meeting of the American Society of Clinical Oncology. ONJ is one of the most common reasons for discontinuing bisphosphonates, with previous reports’ linking the duration of exposure to its development.

"The first cases tend to occur by 12 months. These plateaued by about 36 months, and from that time on there is no continued cases or accrual of new cases," said Dr. Morgan, professor of hematology and head of the myeloma unit at Royal Marsden Hospital, London.

Session moderator Dr. Rafat Abonour, professor of medicine and director of adult clinical research in the cancer center at Indiana University, Indianapolis, said in an interview that IV bisphosphonates seem to be superior to oral ones, with less skeletal-related events and better survival.

"Survival is impressive," he said. "[The] low rate of ONJ is assuring that the benefit-risk ratio is in favor of using zoledronic acid."

The MRC Myeloma IX trial investigators previously reported significant progression-free and overall survival benefits for zoledronic acid over clodronate at 3.7 years’ follow-up (Lancet 2010;376:1965-6). They also found that zoledronic acid significantly reduces the risk of skeletal-related events, even among patients without bone lesions at baseline – a subset generally not considered for bisphosphonate therapy (Lancet Oncol. 2011;12:743-52).

Bisphosphonates such as zoledronic acid inhibit osteoclast-mediated osteolysis, and are used along with chemotherapy to treat bone lesions present in about 70% of patients at diagnosis of multiple myeloma. The optimal duration of use, however, has not been determined.

The current data provide the longest follow-up from the MRC Myeloma IX trial, and further evidence that zoledronic acid also exerts an antimyeloma effect, said Dr. Morgan.

Investigators at 120 centers in the United Kingdom randomly assigned 1,960 patients with newly diagnosed stage I-III multiple myeloma to intravenous zoledronic acid at 4 mg every 21-28 days or oral 1,600 mg clodronate daily plus nonintensive chemotherapy consisting of oral melphalan and prednisone (MP) or attenuated oral cyclophosphamide, thalidomide and dexamethasone (C-TDa), or intensive chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) or C-TD. After first-line treatment, patients were randomly assigned to maintenance therapy with thalidomide at 50 mg/day initially, increasing to 100 mg/day if tolerated, or to no thalidomide maintenance.

Renal failure rates ranged from 5% to 7% in the zoledronic group and from 6% to 7% in the clodronate group. ONJ rates ranged from 2% to 5% among zoledronate patients, compared with 0 to 1% for those who were given clodronate.

The study found that concomitant use of thalidomide seemed to reduce the rate of ONJ, Dr. Morgan noted. "This may reflect part of the mechanism of how ONJ occurs or it may relate to the fact that the responses are greater in the thalidomide-treated group," he added.

Among intensively treated zoledronic acid patients, ONJ rates fell significantly from 4.7% with CVAD to 3.2% with cyclophosphamide, thalidomide and dexamethasone (C-TD) chemotherapy. In the clodronate group, rates fell from 1.1% to 0%.

The same was true for nonintensively treated zoledronic acid patients, with ONJ rates decreasing significantly from 4.7% with melphalan and prednisone to 1.9% with attenuated C-TD, Dr. Morgan said. Rates for clodronate patients were 0.5% for both chemotherapy regimens.

Of note, thalidomide is used less in the United States. Furthermore, most U.S. oncologists use zoledronic acid and pamidronate (Aredia) rather than clodronate in the management of these patients.

Among nine zoledronic acid patients and one clodronate patient with ONJ recovery data, four had complete recovery, two improved, and four had no change, he said. Dental surgery or trauma preceded ONJ in six zoledronic patients.

The low ONJ incidence in the trial is likely due to the ONJ recommendations (Crit. Rev. Oncol. Hematol. 2007;62:148-152) that were disseminated to Myeloma IX investigators in June 2006, Dr. Morgan observed.

To reduce ONJ rates even further, he recommends that all patients receive a comprehensive dental examination before using bisphosphonates. Any unsalvageable teeth should be removed, all invasive dental procedures completed, and optimal periodontal health achieved.

The U.K. MRC funded the trial. Dr. Morgan reported honoraria and other relationships with Celgene, Johnson & Johnson, Merck, Novartis, and other companies. Dr. Abonour reported no conflicts of interest.

CHICAGO – Long-term therapy with monthly zoledronic acid provides sustained survival benefits over daily oral bisphosphonates in multiple myeloma, with no evidence of a cumulative increase in the risk of osteonecrosis of the jaw.

After a median follow-up of 5.8 years in the MRC (U.K. Medical Research Council) Myeloma IX trial, zoledronic acid (Zometa) significantly improved the primary end points of progression-free survival (19 months vs. 18 months; hazard ratio, 0.88; P = .01) and overall survival (51 months vs. 46 months; HR, 0.88; P = .03) compared with oral clodronate. Patients in both arms of the trial received first-line intensive or nonintensive chemotherapy.

The overall cumulative incidence of osteonecrosis of the jaw (ONJ) was low, at 3.7% for zoledronic acid and 0.5% for clodronate (P less than .0001), Dr. Gareth J. Morgan reported at the annual meeting of the American Society of Clinical Oncology. ONJ is one of the most common reasons for discontinuing bisphosphonates, with previous reports’ linking the duration of exposure to its development.

"The first cases tend to occur by 12 months. These plateaued by about 36 months, and from that time on there is no continued cases or accrual of new cases," said Dr. Morgan, professor of hematology and head of the myeloma unit at Royal Marsden Hospital, London.

Session moderator Dr. Rafat Abonour, professor of medicine and director of adult clinical research in the cancer center at Indiana University, Indianapolis, said in an interview that IV bisphosphonates seem to be superior to oral ones, with less skeletal-related events and better survival.

"Survival is impressive," he said. "[The] low rate of ONJ is assuring that the benefit-risk ratio is in favor of using zoledronic acid."

The MRC Myeloma IX trial investigators previously reported significant progression-free and overall survival benefits for zoledronic acid over clodronate at 3.7 years’ follow-up (Lancet 2010;376:1965-6). They also found that zoledronic acid significantly reduces the risk of skeletal-related events, even among patients without bone lesions at baseline – a subset generally not considered for bisphosphonate therapy (Lancet Oncol. 2011;12:743-52).

Bisphosphonates such as zoledronic acid inhibit osteoclast-mediated osteolysis, and are used along with chemotherapy to treat bone lesions present in about 70% of patients at diagnosis of multiple myeloma. The optimal duration of use, however, has not been determined.

The current data provide the longest follow-up from the MRC Myeloma IX trial, and further evidence that zoledronic acid also exerts an antimyeloma effect, said Dr. Morgan.

Investigators at 120 centers in the United Kingdom randomly assigned 1,960 patients with newly diagnosed stage I-III multiple myeloma to intravenous zoledronic acid at 4 mg every 21-28 days or oral 1,600 mg clodronate daily plus nonintensive chemotherapy consisting of oral melphalan and prednisone (MP) or attenuated oral cyclophosphamide, thalidomide and dexamethasone (C-TDa), or intensive chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) or C-TD. After first-line treatment, patients were randomly assigned to maintenance therapy with thalidomide at 50 mg/day initially, increasing to 100 mg/day if tolerated, or to no thalidomide maintenance.

Renal failure rates ranged from 5% to 7% in the zoledronic group and from 6% to 7% in the clodronate group. ONJ rates ranged from 2% to 5% among zoledronate patients, compared with 0 to 1% for those who were given clodronate.

The study found that concomitant use of thalidomide seemed to reduce the rate of ONJ, Dr. Morgan noted. "This may reflect part of the mechanism of how ONJ occurs or it may relate to the fact that the responses are greater in the thalidomide-treated group," he added.

Among intensively treated zoledronic acid patients, ONJ rates fell significantly from 4.7% with CVAD to 3.2% with cyclophosphamide, thalidomide and dexamethasone (C-TD) chemotherapy. In the clodronate group, rates fell from 1.1% to 0%.

The same was true for nonintensively treated zoledronic acid patients, with ONJ rates decreasing significantly from 4.7% with melphalan and prednisone to 1.9% with attenuated C-TD, Dr. Morgan said. Rates for clodronate patients were 0.5% for both chemotherapy regimens.

Of note, thalidomide is used less in the United States. Furthermore, most U.S. oncologists use zoledronic acid and pamidronate (Aredia) rather than clodronate in the management of these patients.

Among nine zoledronic acid patients and one clodronate patient with ONJ recovery data, four had complete recovery, two improved, and four had no change, he said. Dental surgery or trauma preceded ONJ in six zoledronic patients.

The low ONJ incidence in the trial is likely due to the ONJ recommendations (Crit. Rev. Oncol. Hematol. 2007;62:148-152) that were disseminated to Myeloma IX investigators in June 2006, Dr. Morgan observed.

To reduce ONJ rates even further, he recommends that all patients receive a comprehensive dental examination before using bisphosphonates. Any unsalvageable teeth should be removed, all invasive dental procedures completed, and optimal periodontal health achieved.

The U.K. MRC funded the trial. Dr. Morgan reported honoraria and other relationships with Celgene, Johnson & Johnson, Merck, Novartis, and other companies. Dr. Abonour reported no conflicts of interest.

CHICAGO – Long-term therapy with monthly zoledronic acid provides sustained survival benefits over daily oral bisphosphonates in multiple myeloma, with no evidence of a cumulative increase in the risk of osteonecrosis of the jaw.

After a median follow-up of 5.8 years in the MRC (U.K. Medical Research Council) Myeloma IX trial, zoledronic acid (Zometa) significantly improved the primary end points of progression-free survival (19 months vs. 18 months; hazard ratio, 0.88; P = .01) and overall survival (51 months vs. 46 months; HR, 0.88; P = .03) compared with oral clodronate. Patients in both arms of the trial received first-line intensive or nonintensive chemotherapy.

The overall cumulative incidence of osteonecrosis of the jaw (ONJ) was low, at 3.7% for zoledronic acid and 0.5% for clodronate (P less than .0001), Dr. Gareth J. Morgan reported at the annual meeting of the American Society of Clinical Oncology. ONJ is one of the most common reasons for discontinuing bisphosphonates, with previous reports’ linking the duration of exposure to its development.

"The first cases tend to occur by 12 months. These plateaued by about 36 months, and from that time on there is no continued cases or accrual of new cases," said Dr. Morgan, professor of hematology and head of the myeloma unit at Royal Marsden Hospital, London.

Session moderator Dr. Rafat Abonour, professor of medicine and director of adult clinical research in the cancer center at Indiana University, Indianapolis, said in an interview that IV bisphosphonates seem to be superior to oral ones, with less skeletal-related events and better survival.

"Survival is impressive," he said. "[The] low rate of ONJ is assuring that the benefit-risk ratio is in favor of using zoledronic acid."

The MRC Myeloma IX trial investigators previously reported significant progression-free and overall survival benefits for zoledronic acid over clodronate at 3.7 years’ follow-up (Lancet 2010;376:1965-6). They also found that zoledronic acid significantly reduces the risk of skeletal-related events, even among patients without bone lesions at baseline – a subset generally not considered for bisphosphonate therapy (Lancet Oncol. 2011;12:743-52).

Bisphosphonates such as zoledronic acid inhibit osteoclast-mediated osteolysis, and are used along with chemotherapy to treat bone lesions present in about 70% of patients at diagnosis of multiple myeloma. The optimal duration of use, however, has not been determined.

The current data provide the longest follow-up from the MRC Myeloma IX trial, and further evidence that zoledronic acid also exerts an antimyeloma effect, said Dr. Morgan.

Investigators at 120 centers in the United Kingdom randomly assigned 1,960 patients with newly diagnosed stage I-III multiple myeloma to intravenous zoledronic acid at 4 mg every 21-28 days or oral 1,600 mg clodronate daily plus nonintensive chemotherapy consisting of oral melphalan and prednisone (MP) or attenuated oral cyclophosphamide, thalidomide and dexamethasone (C-TDa), or intensive chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin and dexamethasone (CVAD) or C-TD. After first-line treatment, patients were randomly assigned to maintenance therapy with thalidomide at 50 mg/day initially, increasing to 100 mg/day if tolerated, or to no thalidomide maintenance.

Renal failure rates ranged from 5% to 7% in the zoledronic group and from 6% to 7% in the clodronate group. ONJ rates ranged from 2% to 5% among zoledronate patients, compared with 0 to 1% for those who were given clodronate.

The study found that concomitant use of thalidomide seemed to reduce the rate of ONJ, Dr. Morgan noted. "This may reflect part of the mechanism of how ONJ occurs or it may relate to the fact that the responses are greater in the thalidomide-treated group," he added.

Among intensively treated zoledronic acid patients, ONJ rates fell significantly from 4.7% with CVAD to 3.2% with cyclophosphamide, thalidomide and dexamethasone (C-TD) chemotherapy. In the clodronate group, rates fell from 1.1% to 0%.

The same was true for nonintensively treated zoledronic acid patients, with ONJ rates decreasing significantly from 4.7% with melphalan and prednisone to 1.9% with attenuated C-TD, Dr. Morgan said. Rates for clodronate patients were 0.5% for both chemotherapy regimens.

Of note, thalidomide is used less in the United States. Furthermore, most U.S. oncologists use zoledronic acid and pamidronate (Aredia) rather than clodronate in the management of these patients.

Among nine zoledronic acid patients and one clodronate patient with ONJ recovery data, four had complete recovery, two improved, and four had no change, he said. Dental surgery or trauma preceded ONJ in six zoledronic patients.

The low ONJ incidence in the trial is likely due to the ONJ recommendations (Crit. Rev. Oncol. Hematol. 2007;62:148-152) that were disseminated to Myeloma IX investigators in June 2006, Dr. Morgan observed.

To reduce ONJ rates even further, he recommends that all patients receive a comprehensive dental examination before using bisphosphonates. Any unsalvageable teeth should be removed, all invasive dental procedures completed, and optimal periodontal health achieved.

The U.K. MRC funded the trial. Dr. Morgan reported honoraria and other relationships with Celgene, Johnson & Johnson, Merck, Novartis, and other companies. Dr. Abonour reported no conflicts of interest.

Transthoracic two-dimensional echocardiography appears to be inadequate for identifying cardiomyopathy in adults who survive childhood cancer, according to a cross-sectional study published online July 16 in the Journal of Clinical Oncology.

Compared with cardiac magnetic resonance imaging (CMRI), which is considered the reference standard to which other cardiac imaging techniques are compared, 2-D echocardiography had a sensitivity of only 25% and a false-negative rate of 75% in identifying cardiomyopathy in a study of 134 adult survivors of childhood cancer, said Dr. Gregory T. Armstrong of the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, Memphis, and his associates.

In these relatively young and apparently healthy study subjects who had never been diagnosed as having any cardiac abnormality, nearly half (48%) were found to have the reduced cardiac mass indicative of cancer therapy–related injury. And fully 11% of subjects who were judged to have a normal ejection fraction (EF) on 2-D echocardiography were actually proved to have an EF of less than 50% on CMRI, the researchers noted.

That number easily could have been higher, but there happened to be a low absolute number of patients (16) with this degree of EF impairment in the small cohort, they pointed out.

Adults who survive childhood cancer are at risk for cardiomyopathy because of their exposure to chemotherapy and radiotherapy. Current guidelines recommend screening such adults by transthoracic 2-D echocardiography because it is noninvasive, widely available, and less expensive than other techniques.

However, the quality of the acoustic windows obtained on 2-D echo varies widely, and the method depends on geometric assumptions that may not be valid in patients who have dilated or remodeled ventricles. Three-dimensional echocardiography yields somewhat more accurate results but is not as widely available. CMRI is the most accurate noninvasive imaging technique, but is more expensive and is even less widely available, Dr. Armstrong and his colleagues explained.

They assessed the accuracy of 2-D and 3-D echocardiography against CMRI as a screen for cardiomyopathy in a longitudinal cohort of 134 adults who had been treated at St. Jude’s for childhood cancer 18-38 years earlier. All had received chest-directed radiotherapy and/or anthracycline chemotherapy, both of which are known to impair cardiac function during treatment and to raise the risk of reduced left ventricular function later in life.

The most common pediatric malignancies were acute lymphoblastic leukemia (44 subjects) and Hodgkin’s lymphoma (37 subjects).

The median age at echocardiographic screening in adulthood was 39 years (range, 22-53 years).

Of the study subjects, 20 were unable to complete CMRI for a variety of reasons. Future studies that compare imaging techniques should take into consideration this relatively high noncompletion rate (15%) for CMRI, especially in cost-benefit analyses, Dr. Armstrong and his colleagues said (J. Clin. Oncol. 2012 July 16 [doi:10.1200/JCO.2011.40.3584]).

In the remaining 114 subjects, 2-D echocardiography consistently overestimated left ventricular ejection fraction (LVEF) and underestimated both end-systolic and end-diastolic ventricular volumes.

In all, 16 subjects were identified as having markedly decreased LVEF (50% or more) by CMRI, but only 4 of them were so identified by 2-D echocardiography and only 11 of them by 3-D echocardiography.

Compared with CMRI, the sensitivity of 2-D echocardiography was only 25%; that of 3-D echo was better but still inadequate, at only 53%. And false-negative rates were high with both 2-D echocardiography (75%) and 3-D echocardiography (47%).

Of particular concern was the finding that on CMRI, 32% of the study subjects had an LVEF that was well below normal. The rate in the subgroup of patients who had received both chest irradiation and anthracycline during childhood cancer treatment was even higher, at 42%.

A total of 48% of the study subjects had a cardiac mass that was at least 2 standard deviations below normal for their age and sex, a clear sign of cardiotoxicity from their childhood cancer treatment. "Notably, even patients who received less than 150 mg/m² of anthracyclines had a high prevalence of reduced EF (27%), stroke volume (29%), or cardiac mass (56%)," the investigators said.

Estimates derived from Medicare data suggest that at roughly $449 each, CMRI examinations cost about $217 more than does echocardiography ($232 each). Given the high rate of cardiomyopathy discovered in this cohort, and the poor sensitivity of echocardiography as a screening tool, this cost difference may be small enough to warrant a switch in the current screening recommendations from echocardiography to CMRI.

The additional cost of a CMRI-only screening strategy per case of cardiotoxicity correctly identified would be only $1,973, they noted.

The study findings suggest that in this high-risk patient population that was exposed to cardiotoxic therapy during childhood, "consideration should be given to referring survivors with an EF of 50%-59% on [2-D echocardiography] for comprehensive cardiology assessment that includes cardiac history, symptom index, and examination; biomarker assessment; consideration of [CMRI]; functional assessment by treadmill testing; and possibly medical therapy to prevent progression of disease," Dr. Armstrong and his associates said.

This study was supported by the American Society of Clinical Oncology and the American Lebanese-Syrian Associated Charities. Dr. Armstrong’s associates reported ties to General Electric and Philips Healthcare.

Transthoracic two-dimensional echocardiography appears to be inadequate for identifying cardiomyopathy in adults who survive childhood cancer, according to a cross-sectional study published online July 16 in the Journal of Clinical Oncology.

Compared with cardiac magnetic resonance imaging (CMRI), which is considered the reference standard to which other cardiac imaging techniques are compared, 2-D echocardiography had a sensitivity of only 25% and a false-negative rate of 75% in identifying cardiomyopathy in a study of 134 adult survivors of childhood cancer, said Dr. Gregory T. Armstrong of the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, Memphis, and his associates.

In these relatively young and apparently healthy study subjects who had never been diagnosed as having any cardiac abnormality, nearly half (48%) were found to have the reduced cardiac mass indicative of cancer therapy–related injury. And fully 11% of subjects who were judged to have a normal ejection fraction (EF) on 2-D echocardiography were actually proved to have an EF of less than 50% on CMRI, the researchers noted.

That number easily could have been higher, but there happened to be a low absolute number of patients (16) with this degree of EF impairment in the small cohort, they pointed out.

Adults who survive childhood cancer are at risk for cardiomyopathy because of their exposure to chemotherapy and radiotherapy. Current guidelines recommend screening such adults by transthoracic 2-D echocardiography because it is noninvasive, widely available, and less expensive than other techniques.

However, the quality of the acoustic windows obtained on 2-D echo varies widely, and the method depends on geometric assumptions that may not be valid in patients who have dilated or remodeled ventricles. Three-dimensional echocardiography yields somewhat more accurate results but is not as widely available. CMRI is the most accurate noninvasive imaging technique, but is more expensive and is even less widely available, Dr. Armstrong and his colleagues explained.

They assessed the accuracy of 2-D and 3-D echocardiography against CMRI as a screen for cardiomyopathy in a longitudinal cohort of 134 adults who had been treated at St. Jude’s for childhood cancer 18-38 years earlier. All had received chest-directed radiotherapy and/or anthracycline chemotherapy, both of which are known to impair cardiac function during treatment and to raise the risk of reduced left ventricular function later in life.

The most common pediatric malignancies were acute lymphoblastic leukemia (44 subjects) and Hodgkin’s lymphoma (37 subjects).

The median age at echocardiographic screening in adulthood was 39 years (range, 22-53 years).

Of the study subjects, 20 were unable to complete CMRI for a variety of reasons. Future studies that compare imaging techniques should take into consideration this relatively high noncompletion rate (15%) for CMRI, especially in cost-benefit analyses, Dr. Armstrong and his colleagues said (J. Clin. Oncol. 2012 July 16 [doi:10.1200/JCO.2011.40.3584]).

In the remaining 114 subjects, 2-D echocardiography consistently overestimated left ventricular ejection fraction (LVEF) and underestimated both end-systolic and end-diastolic ventricular volumes.

In all, 16 subjects were identified as having markedly decreased LVEF (50% or more) by CMRI, but only 4 of them were so identified by 2-D echocardiography and only 11 of them by 3-D echocardiography.

Compared with CMRI, the sensitivity of 2-D echocardiography was only 25%; that of 3-D echo was better but still inadequate, at only 53%. And false-negative rates were high with both 2-D echocardiography (75%) and 3-D echocardiography (47%).

Of particular concern was the finding that on CMRI, 32% of the study subjects had an LVEF that was well below normal. The rate in the subgroup of patients who had received both chest irradiation and anthracycline during childhood cancer treatment was even higher, at 42%.

A total of 48% of the study subjects had a cardiac mass that was at least 2 standard deviations below normal for their age and sex, a clear sign of cardiotoxicity from their childhood cancer treatment. "Notably, even patients who received less than 150 mg/m² of anthracyclines had a high prevalence of reduced EF (27%), stroke volume (29%), or cardiac mass (56%)," the investigators said.

Estimates derived from Medicare data suggest that at roughly $449 each, CMRI examinations cost about $217 more than does echocardiography ($232 each). Given the high rate of cardiomyopathy discovered in this cohort, and the poor sensitivity of echocardiography as a screening tool, this cost difference may be small enough to warrant a switch in the current screening recommendations from echocardiography to CMRI.

The additional cost of a CMRI-only screening strategy per case of cardiotoxicity correctly identified would be only $1,973, they noted.

The study findings suggest that in this high-risk patient population that was exposed to cardiotoxic therapy during childhood, "consideration should be given to referring survivors with an EF of 50%-59% on [2-D echocardiography] for comprehensive cardiology assessment that includes cardiac history, symptom index, and examination; biomarker assessment; consideration of [CMRI]; functional assessment by treadmill testing; and possibly medical therapy to prevent progression of disease," Dr. Armstrong and his associates said.

This study was supported by the American Society of Clinical Oncology and the American Lebanese-Syrian Associated Charities. Dr. Armstrong’s associates reported ties to General Electric and Philips Healthcare.

Transthoracic two-dimensional echocardiography appears to be inadequate for identifying cardiomyopathy in adults who survive childhood cancer, according to a cross-sectional study published online July 16 in the Journal of Clinical Oncology.

Compared with cardiac magnetic resonance imaging (CMRI), which is considered the reference standard to which other cardiac imaging techniques are compared, 2-D echocardiography had a sensitivity of only 25% and a false-negative rate of 75% in identifying cardiomyopathy in a study of 134 adult survivors of childhood cancer, said Dr. Gregory T. Armstrong of the department of epidemiology and cancer control at St. Jude Children’s Research Hospital, Memphis, and his associates.

In these relatively young and apparently healthy study subjects who had never been diagnosed as having any cardiac abnormality, nearly half (48%) were found to have the reduced cardiac mass indicative of cancer therapy–related injury. And fully 11% of subjects who were judged to have a normal ejection fraction (EF) on 2-D echocardiography were actually proved to have an EF of less than 50% on CMRI, the researchers noted.

That number easily could have been higher, but there happened to be a low absolute number of patients (16) with this degree of EF impairment in the small cohort, they pointed out.

Adults who survive childhood cancer are at risk for cardiomyopathy because of their exposure to chemotherapy and radiotherapy. Current guidelines recommend screening such adults by transthoracic 2-D echocardiography because it is noninvasive, widely available, and less expensive than other techniques.

However, the quality of the acoustic windows obtained on 2-D echo varies widely, and the method depends on geometric assumptions that may not be valid in patients who have dilated or remodeled ventricles. Three-dimensional echocardiography yields somewhat more accurate results but is not as widely available. CMRI is the most accurate noninvasive imaging technique, but is more expensive and is even less widely available, Dr. Armstrong and his colleagues explained.

They assessed the accuracy of 2-D and 3-D echocardiography against CMRI as a screen for cardiomyopathy in a longitudinal cohort of 134 adults who had been treated at St. Jude’s for childhood cancer 18-38 years earlier. All had received chest-directed radiotherapy and/or anthracycline chemotherapy, both of which are known to impair cardiac function during treatment and to raise the risk of reduced left ventricular function later in life.

The most common pediatric malignancies were acute lymphoblastic leukemia (44 subjects) and Hodgkin’s lymphoma (37 subjects).

The median age at echocardiographic screening in adulthood was 39 years (range, 22-53 years).

Of the study subjects, 20 were unable to complete CMRI for a variety of reasons. Future studies that compare imaging techniques should take into consideration this relatively high noncompletion rate (15%) for CMRI, especially in cost-benefit analyses, Dr. Armstrong and his colleagues said (J. Clin. Oncol. 2012 July 16 [doi:10.1200/JCO.2011.40.3584]).

In the remaining 114 subjects, 2-D echocardiography consistently overestimated left ventricular ejection fraction (LVEF) and underestimated both end-systolic and end-diastolic ventricular volumes.

In all, 16 subjects were identified as having markedly decreased LVEF (50% or more) by CMRI, but only 4 of them were so identified by 2-D echocardiography and only 11 of them by 3-D echocardiography.

Compared with CMRI, the sensitivity of 2-D echocardiography was only 25%; that of 3-D echo was better but still inadequate, at only 53%. And false-negative rates were high with both 2-D echocardiography (75%) and 3-D echocardiography (47%).

Of particular concern was the finding that on CMRI, 32% of the study subjects had an LVEF that was well below normal. The rate in the subgroup of patients who had received both chest irradiation and anthracycline during childhood cancer treatment was even higher, at 42%.

A total of 48% of the study subjects had a cardiac mass that was at least 2 standard deviations below normal for their age and sex, a clear sign of cardiotoxicity from their childhood cancer treatment. "Notably, even patients who received less than 150 mg/m² of anthracyclines had a high prevalence of reduced EF (27%), stroke volume (29%), or cardiac mass (56%)," the investigators said.

Estimates derived from Medicare data suggest that at roughly $449 each, CMRI examinations cost about $217 more than does echocardiography ($232 each). Given the high rate of cardiomyopathy discovered in this cohort, and the poor sensitivity of echocardiography as a screening tool, this cost difference may be small enough to warrant a switch in the current screening recommendations from echocardiography to CMRI.

The additional cost of a CMRI-only screening strategy per case of cardiotoxicity correctly identified would be only $1,973, they noted.

The study findings suggest that in this high-risk patient population that was exposed to cardiotoxic therapy during childhood, "consideration should be given to referring survivors with an EF of 50%-59% on [2-D echocardiography] for comprehensive cardiology assessment that includes cardiac history, symptom index, and examination; biomarker assessment; consideration of [CMRI]; functional assessment by treadmill testing; and possibly medical therapy to prevent progression of disease," Dr. Armstrong and his associates said.

This study was supported by the American Society of Clinical Oncology and the American Lebanese-Syrian Associated Charities. Dr. Armstrong’s associates reported ties to General Electric and Philips Healthcare.

NEW ORLEANS – Most middle-age U.S. cancer survivors don’t meet current national physical activity guidelines, according to a large, in-depth telephone survey.

This represents an opportunity for intervention. Evidence indicates that cancer survivors who meet physical activity guidelines experience improved quality of life and health outcomes, according to Pratibha Parelkar, a biostatistician at the University of Texas M.D. Anderson Cancer Center, Houston.

Those guidelines call for 30 minutes or more of moderate physical activity at least 5 days per week, or 20 minutes of vigorous physical activity at least 3 days per week, she noted at the annual meeting of the Society of Behavioral Medicine.

She analyzed data from the 2009 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention. Of the 8,665 respondents aged 45-64 years who were at least 1 year post diagnosis of breast, prostate, colon, cervix, or bladder cancer or melanoma, more than half (53%) were not meeting physical activity guidelines.

In a multivariate logistic regression analysis, several characteristics proved to be independently associated with not meeting the recommendations for physical activity. Blacks were 2.1-fold more likely than were whites to not meet the guidelines. Not being a college graduate was associated with a 39% increased risk. Subjects who were overweight were 32% more likely and those who were obese were 2.5-fold more likely than were normal-weight cancer survivors to not meet the physical activity guidelines.

Ms. Parelkar’s study was funded by M.D. Anderson. She reported having no financial conflicts.

NEW ORLEANS – Most middle-age U.S. cancer survivors don’t meet current national physical activity guidelines, according to a large, in-depth telephone survey.

This represents an opportunity for intervention. Evidence indicates that cancer survivors who meet physical activity guidelines experience improved quality of life and health outcomes, according to Pratibha Parelkar, a biostatistician at the University of Texas M.D. Anderson Cancer Center, Houston.

Those guidelines call for 30 minutes or more of moderate physical activity at least 5 days per week, or 20 minutes of vigorous physical activity at least 3 days per week, she noted at the annual meeting of the Society of Behavioral Medicine.

She analyzed data from the 2009 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention. Of the 8,665 respondents aged 45-64 years who were at least 1 year post diagnosis of breast, prostate, colon, cervix, or bladder cancer or melanoma, more than half (53%) were not meeting physical activity guidelines.

In a multivariate logistic regression analysis, several characteristics proved to be independently associated with not meeting the recommendations for physical activity. Blacks were 2.1-fold more likely than were whites to not meet the guidelines. Not being a college graduate was associated with a 39% increased risk. Subjects who were overweight were 32% more likely and those who were obese were 2.5-fold more likely than were normal-weight cancer survivors to not meet the physical activity guidelines.

Ms. Parelkar’s study was funded by M.D. Anderson. She reported having no financial conflicts.

NEW ORLEANS – Most middle-age U.S. cancer survivors don’t meet current national physical activity guidelines, according to a large, in-depth telephone survey.

This represents an opportunity for intervention. Evidence indicates that cancer survivors who meet physical activity guidelines experience improved quality of life and health outcomes, according to Pratibha Parelkar, a biostatistician at the University of Texas M.D. Anderson Cancer Center, Houston.

Those guidelines call for 30 minutes or more of moderate physical activity at least 5 days per week, or 20 minutes of vigorous physical activity at least 3 days per week, she noted at the annual meeting of the Society of Behavioral Medicine.

She analyzed data from the 2009 Behavioral Risk Factor Surveillance System survey conducted by the Centers for Disease Control and Prevention. Of the 8,665 respondents aged 45-64 years who were at least 1 year post diagnosis of breast, prostate, colon, cervix, or bladder cancer or melanoma, more than half (53%) were not meeting physical activity guidelines.

In a multivariate logistic regression analysis, several characteristics proved to be independently associated with not meeting the recommendations for physical activity. Blacks were 2.1-fold more likely than were whites to not meet the guidelines. Not being a college graduate was associated with a 39% increased risk. Subjects who were overweight were 32% more likely and those who were obese were 2.5-fold more likely than were normal-weight cancer survivors to not meet the physical activity guidelines.

Ms. Parelkar’s study was funded by M.D. Anderson. She reported having no financial conflicts.

CHICAGO – Long-term platinum exposure may explain higher rates of certain late adverse effects in men who have undergone treatment for testicular cancer, investigators reported based on a longitudinal study.

Among 96 consecutive men treated with cisplatin for testicular cancer, serum platinum levels 5 years later were 14% higher in those with elevated versus normal blood pressure and 16% higher in those with paresthesia versus those without it.

Dr. Hink Boer and his colleagues collected two or three serum samples and a 24-hour urine sample from the men at various time points after chemotherapy out to 13 years (median, 5 years) for platinum measurement.

The men had a median age of 29 years at the start of treatment, according to results reported in a poster presentation at the annual meeting of the American Society of Clinical Oncology. The median absolute cumulative cisplatin dose was 809 mg.

The findings are especially important as these survivors are young men who "have their whole life ahead of them, actually. Survivor care is very much focused on relapse detection, of course. In the last decade, I think there is more attention on the delayed effects," Dr. Boer, a research fellow in medical oncology at the University of Groningen in the Netherlands, said in an interview.

A population pharmacokinetic model using measured serum platinum concentration and urinary excretion rate, as well as administered cisplatin dosage, age, body surface area, height, and weight, suggested that the mean terminal half-life of platinum in serum was 3.7 years, Dr. Boer reported.

Platinum levels fell steadily and in exponential fashion with time after chemotherapy but were still detectable 13 years later. Serum platinum levels at 3 years and at 5 years after chemotherapy were significantly higher in men administered a higher total dose of cisplatin and in men having lower renal clearance, he said.

Analyses of long-term toxicity showed that, compared with their counterparts with lower blood pressure, men with a blood pressure of at least 130/85 mm Hg or on antihypertensive medication had higher mean serum platinum levels at 3 years (420 vs. 366 pg/g, P = .045) and at 5 years (210 vs. 185 pg/g, P = .04), as well as a higher platinum area under the curve (AUC) for years 1-5 (1,071 vs. 945 pg/g × 10³ × day, P = .04).

Similarly, compared with their counterparts who did not have paresthesia, men having this adverse effect had higher mean serum platinum levels at 3 years (456 vs. 387 pg/g, P = .02) and at 5 years (227 vs. 195 pg/g, P = .02), as well as a higher platinum AUC for years 1-5 (1,144 vs. 996 pg/g × 10³ × day, P = .02).

In contrast, men with secondary Raynaud disease and men with endothelial damage as assessed from von Willebrand factor levels did not have significantly higher serum platinum levels than their respective counterparts, Dr. Boer said.

"It is a well-known problem now that the chemotherapy has its late effects, and we wanted to look to see if these very small concentrations ... have any relationship with these late toxicities," he said. "If you look at these data, you could assume that there is a relationship, a very small concentration but still, it might have an effect."

"The chemotherapy is very successful, of course; you don’t want to change it. The cure rates are very high in testicular cancer patients," he added. "At the moment it is not possible to get the platinum out of the body. It is not technically possible to chelate it or something.

"But you have to think about it – it could be a mechanism, so it is worthwhile to do more studies on this. Perhaps in the future, it will be possible to chelate it and get it out, if we can confirm that this is really an etiological mechanism," he said.

Current practice at his institution for these patients is regular examinations with special focus on cardiovascular risk factors such as blood pressure and cholesterol. "We are trying to bring more structure in this care and to pay more attention to the late effects. I think [the patients] deserve it because they are so young," Dr. Boer said.

Discussant Dr. Kim Allyson Margolin of the University of Washington, Seattle, noted that accumulating research is casting doubt on the view that this chemotherapy has minimal late effects. However, despite the finding of an association between persistent free platinum and late toxicity, "we don’t know whether the relationship of prior platinum exposure, just by doses given or something different about how the body handles the platinum related to renal function or metabolic polymorphisms, is responsible"

The study is "very interesting and provocative," Dr. Margolin concluded, "but we need more data. Pharmacologic investigations are still needed to enhance the quality of life for this growing number of germ cell tumor survivors."

Although the study focused on serum, Dr. Boer noted that platinum can be found in other tissues as well. "In the ganglia, for example, and also in bone, fat, and the liver ... it’s ... not really known if the platinum in these body compartments is reactive or not. It is really a topic that deserves more research," he said.

Dr. Boer disclosed that he had no relevant conflicts of interest. Dr. Margolin disclosed that she is a consultant to Bristol-Myers Squibb, Genentech, and Johnson & Johnson.

CHICAGO – Long-term platinum exposure may explain higher rates of certain late adverse effects in men who have undergone treatment for testicular cancer, investigators reported based on a longitudinal study.

Among 96 consecutive men treated with cisplatin for testicular cancer, serum platinum levels 5 years later were 14% higher in those with elevated versus normal blood pressure and 16% higher in those with paresthesia versus those without it.

Dr. Hink Boer and his colleagues collected two or three serum samples and a 24-hour urine sample from the men at various time points after chemotherapy out to 13 years (median, 5 years) for platinum measurement.

The men had a median age of 29 years at the start of treatment, according to results reported in a poster presentation at the annual meeting of the American Society of Clinical Oncology. The median absolute cumulative cisplatin dose was 809 mg.

The findings are especially important as these survivors are young men who "have their whole life ahead of them, actually. Survivor care is very much focused on relapse detection, of course. In the last decade, I think there is more attention on the delayed effects," Dr. Boer, a research fellow in medical oncology at the University of Groningen in the Netherlands, said in an interview.

A population pharmacokinetic model using measured serum platinum concentration and urinary excretion rate, as well as administered cisplatin dosage, age, body surface area, height, and weight, suggested that the mean terminal half-life of platinum in serum was 3.7 years, Dr. Boer reported.

Platinum levels fell steadily and in exponential fashion with time after chemotherapy but were still detectable 13 years later. Serum platinum levels at 3 years and at 5 years after chemotherapy were significantly higher in men administered a higher total dose of cisplatin and in men having lower renal clearance, he said.

Analyses of long-term toxicity showed that, compared with their counterparts with lower blood pressure, men with a blood pressure of at least 130/85 mm Hg or on antihypertensive medication had higher mean serum platinum levels at 3 years (420 vs. 366 pg/g, P = .045) and at 5 years (210 vs. 185 pg/g, P = .04), as well as a higher platinum area under the curve (AUC) for years 1-5 (1,071 vs. 945 pg/g × 10³ × day, P = .04).

Similarly, compared with their counterparts who did not have paresthesia, men having this adverse effect had higher mean serum platinum levels at 3 years (456 vs. 387 pg/g, P = .02) and at 5 years (227 vs. 195 pg/g, P = .02), as well as a higher platinum AUC for years 1-5 (1,144 vs. 996 pg/g × 10³ × day, P = .02).

In contrast, men with secondary Raynaud disease and men with endothelial damage as assessed from von Willebrand factor levels did not have significantly higher serum platinum levels than their respective counterparts, Dr. Boer said.

"It is a well-known problem now that the chemotherapy has its late effects, and we wanted to look to see if these very small concentrations ... have any relationship with these late toxicities," he said. "If you look at these data, you could assume that there is a relationship, a very small concentration but still, it might have an effect."

"The chemotherapy is very successful, of course; you don’t want to change it. The cure rates are very high in testicular cancer patients," he added. "At the moment it is not possible to get the platinum out of the body. It is not technically possible to chelate it or something.

"But you have to think about it – it could be a mechanism, so it is worthwhile to do more studies on this. Perhaps in the future, it will be possible to chelate it and get it out, if we can confirm that this is really an etiological mechanism," he said.

Current practice at his institution for these patients is regular examinations with special focus on cardiovascular risk factors such as blood pressure and cholesterol. "We are trying to bring more structure in this care and to pay more attention to the late effects. I think [the patients] deserve it because they are so young," Dr. Boer said.

Discussant Dr. Kim Allyson Margolin of the University of Washington, Seattle, noted that accumulating research is casting doubt on the view that this chemotherapy has minimal late effects. However, despite the finding of an association between persistent free platinum and late toxicity, "we don’t know whether the relationship of prior platinum exposure, just by doses given or something different about how the body handles the platinum related to renal function or metabolic polymorphisms, is responsible"

The study is "very interesting and provocative," Dr. Margolin concluded, "but we need more data. Pharmacologic investigations are still needed to enhance the quality of life for this growing number of germ cell tumor survivors."

Although the study focused on serum, Dr. Boer noted that platinum can be found in other tissues as well. "In the ganglia, for example, and also in bone, fat, and the liver ... it’s ... not really known if the platinum in these body compartments is reactive or not. It is really a topic that deserves more research," he said.

Dr. Boer disclosed that he had no relevant conflicts of interest. Dr. Margolin disclosed that she is a consultant to Bristol-Myers Squibb, Genentech, and Johnson & Johnson.

CHICAGO – Long-term platinum exposure may explain higher rates of certain late adverse effects in men who have undergone treatment for testicular cancer, investigators reported based on a longitudinal study.

Among 96 consecutive men treated with cisplatin for testicular cancer, serum platinum levels 5 years later were 14% higher in those with elevated versus normal blood pressure and 16% higher in those with paresthesia versus those without it.

Dr. Hink Boer and his colleagues collected two or three serum samples and a 24-hour urine sample from the men at various time points after chemotherapy out to 13 years (median, 5 years) for platinum measurement.

The men had a median age of 29 years at the start of treatment, according to results reported in a poster presentation at the annual meeting of the American Society of Clinical Oncology. The median absolute cumulative cisplatin dose was 809 mg.

The findings are especially important as these survivors are young men who "have their whole life ahead of them, actually. Survivor care is very much focused on relapse detection, of course. In the last decade, I think there is more attention on the delayed effects," Dr. Boer, a research fellow in medical oncology at the University of Groningen in the Netherlands, said in an interview.

A population pharmacokinetic model using measured serum platinum concentration and urinary excretion rate, as well as administered cisplatin dosage, age, body surface area, height, and weight, suggested that the mean terminal half-life of platinum in serum was 3.7 years, Dr. Boer reported.

Platinum levels fell steadily and in exponential fashion with time after chemotherapy but were still detectable 13 years later. Serum platinum levels at 3 years and at 5 years after chemotherapy were significantly higher in men administered a higher total dose of cisplatin and in men having lower renal clearance, he said.

Analyses of long-term toxicity showed that, compared with their counterparts with lower blood pressure, men with a blood pressure of at least 130/85 mm Hg or on antihypertensive medication had higher mean serum platinum levels at 3 years (420 vs. 366 pg/g, P = .045) and at 5 years (210 vs. 185 pg/g, P = .04), as well as a higher platinum area under the curve (AUC) for years 1-5 (1,071 vs. 945 pg/g × 10³ × day, P = .04).

Similarly, compared with their counterparts who did not have paresthesia, men having this adverse effect had higher mean serum platinum levels at 3 years (456 vs. 387 pg/g, P = .02) and at 5 years (227 vs. 195 pg/g, P = .02), as well as a higher platinum AUC for years 1-5 (1,144 vs. 996 pg/g × 10³ × day, P = .02).

In contrast, men with secondary Raynaud disease and men with endothelial damage as assessed from von Willebrand factor levels did not have significantly higher serum platinum levels than their respective counterparts, Dr. Boer said.

"It is a well-known problem now that the chemotherapy has its late effects, and we wanted to look to see if these very small concentrations ... have any relationship with these late toxicities," he said. "If you look at these data, you could assume that there is a relationship, a very small concentration but still, it might have an effect."

"The chemotherapy is very successful, of course; you don’t want to change it. The cure rates are very high in testicular cancer patients," he added. "At the moment it is not possible to get the platinum out of the body. It is not technically possible to chelate it or something.

"But you have to think about it – it could be a mechanism, so it is worthwhile to do more studies on this. Perhaps in the future, it will be possible to chelate it and get it out, if we can confirm that this is really an etiological mechanism," he said.

Current practice at his institution for these patients is regular examinations with special focus on cardiovascular risk factors such as blood pressure and cholesterol. "We are trying to bring more structure in this care and to pay more attention to the late effects. I think [the patients] deserve it because they are so young," Dr. Boer said.

Discussant Dr. Kim Allyson Margolin of the University of Washington, Seattle, noted that accumulating research is casting doubt on the view that this chemotherapy has minimal late effects. However, despite the finding of an association between persistent free platinum and late toxicity, "we don’t know whether the relationship of prior platinum exposure, just by doses given or something different about how the body handles the platinum related to renal function or metabolic polymorphisms, is responsible"

The study is "very interesting and provocative," Dr. Margolin concluded, "but we need more data. Pharmacologic investigations are still needed to enhance the quality of life for this growing number of germ cell tumor survivors."

Although the study focused on serum, Dr. Boer noted that platinum can be found in other tissues as well. "In the ganglia, for example, and also in bone, fat, and the liver ... it’s ... not really known if the platinum in these body compartments is reactive or not. It is really a topic that deserves more research," he said.

Dr. Boer disclosed that he had no relevant conflicts of interest. Dr. Margolin disclosed that she is a consultant to Bristol-Myers Squibb, Genentech, and Johnson & Johnson.