CASE

Your patient is a 26-year-old G0 woman who has a long history of progressively worsening dysmenorrhea, pelvic pain, and dyspareunia. In the recent past, she was treated with nonsteroidal anti-inflammatory drugs, a cyclic estrogen-progestin contraceptive, and a continuous estrogen-progestin contraceptive—in that order, and without appreciable relief of the pain.

Recently, the woman underwent laparoscopy, which demonstrated Stage-II endometriosis, which was ablated.

What would you prescribe for her postoperatively to alleviate symptoms?

Endometriosis will be diagnosed in approximately 8% of women of reproductive age.¹ Pelvic pain, dysmenorrhea, and deep dyspareunia are common symptoms of endometriosis that interfere with quality of life.

Endometriosis is a chronic disease best managed by developing a life-long treatment plan. Following laparoscopic diagnosis and treatment, many experts strongly recommend postoperative hormone-suppressive therapy to reduce the risk that severe pelvic pain will recur, requiring re-operation.

Options for postoperative hormonal treatment of endometriosis include:

• an estrogen–progestin contraceptive
• a progestin (norethindrone acetate [NEA]; depot medroxyprogesterone acetate [DMPA]; oral medroxyprogesterone acetate; the levonorgestrel-releasing intrauterine system [LNG-IUS; Mirena]; and the progestin-releasing implant [Implanon])
• a gonadotropin-releasing hormone (GnRH) agonist (depot leuprolide [Depot Lupron]; nafarelin nasal spray [Synarel]).

CASE Continued

Considering that both cyclic and continuous estrogen-progestin contraceptives have already failed to provide adequate pain relief for your patient, you know that you should offer an alternative to her. Taking into account that progestins are significantly less costly than a GnRH agonist, a progestin formulation might, for her, be considered a first-line postoperative treatment of symptoms of endometriosis.

Options when considering a progestin

Norethindrone acetate

This agent is available in a single formulation: a 5-mg tablet; however, dosages ranging from 2.5 mg/d (half of a tablet) to 15 mg/d have been reported to be effective for relieving pain caused by endometriosis.

What is it? NEA is an androgenic progestin that suppresses luteinizing hormone and follicle-stimulating hormone, thus reducing production of ovarian estrogen. In the absence of ovarian estrogen, endometriosis lesions atrophy. In addition, NEA binds to, and stimulates, endometrial progestin and androgen receptors, resulting in decidualization and atrophy of both eutopic and ectopic endometrial tissue.

Importantly, NEA does not appear to cause bone loss, a phenomenon that is common with agents such as the GnRH agonists or DPMA.^2-4

The research record. One randomized study, two pilot studies, and one large observational study have reported that NEA is effective for pelvic pain caused by endometriosis.

In the randomized trial, 90 women who had moderate or severe pelvic pain and rectovaginal endometriosis, and who remained symptomatic after conservative surgery, were randomized to receive NEA, 2.5 mg/d, or a low-dose estrogen-progestin contraceptive (ethinyl estradiol, 10 μg, plus cyproterone acetate, 3 mg) daily for 12 months.⁵ Both treatment groups reported significant and similar decreases in dysmenorrhea, deep dyspareunia, non-menstrual pain and dyschezia.

In a small pilot study, 40 women who had pelvic pain and colorectal endometriosis were treated with NEA 2.5 mg/d for 12 months. The drug produced significant improvement in dysmenorrhea, pelvic pain, deep dyspareunia, dyschezia, and cyclic rectal bleeding.⁶

In another pilot study, women who had pelvic pain and rectovaginal endometriosis were treated with either an aromatase inhibitor (letrozole, 2.5 mg/d) plus NEA (2.5 mg/d) or NEA (2.5 mg/d) alone for 6 months. Both treatments resulted in a significant improvement in pelvic pain and deep dyspareunia. Improvement in pain scores was greater with letrozole plus NEA; patients were more satisfied with NEA monotherapy than with the combined letrozole-NEA treatment, however, because the former was associated with fewer side effects.⁷

In a large (n=194) observational study of the postoperative use of NEA in young women with pelvic pain and endometriosis, NEA at dosages as high as 15 mg/d significantly diminished pelvic pain and self-reported menstrual bleeding. All subjects were started on a dosage of 5 mg/d, which was increased in 2.5-mg increments every 2 weeks to achieve the goals of amenorrhea and a lessening of pelvic pain; the maximum dosage administered was 15 mg/d. Mean duration of NEA use was 13 months; 75% of subjects took the maximum prescribed dosage of 15 mg at some point during treatment. The most commonly reported side effects were weight gain (16% of women); acne (10%); mood lability (9%); and vasomotor symptoms (8%).⁸

In summary. NEA is effective for treating pelvic pain caused by endometriosis at dosages from 2.5 mg/d to 15 mg/d. An important goal of treatment is a decrease in pain symptoms and amenorrhea; a dosage of 2.5 mg is often insufficient to reliably achieve both of those objectives.

In my practice I begin therapy at a dosage of 5 mg/d; the drug is effective for most patients at that dosage. If 5 mg/d does not reduce pain, I increase the dosage by 2.5 mg (half of a tablet) daily every 4 weeks, to a maximum dosage of 10 mg/d (two tablets). If that dosage is ineffective, I usually discontinue NEA and switch to a GnRH agonist.

Depot medroxyprogesterone acetate; oral medroxy-progesterone acetate

DMPA is available in two FDA-approved formulations:

• a 150-mg dose given by intramuscular injection every 3 months
• a 104-mg dose given by subcutaneous injection every 3 months.

Research. The results of two large clinical trials, comprising a total of more than 550 subjects, showed that DMPA (104 mg, SC, every 3 months) and depot leuprolide (11.25 mg, IM, every 3 months or 3.75 mg, monthly) were each equally effective in relieving dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and pelvic induration in women who had endometriosis.^9,10

DMPA was associated with a greater rate of episodes of irregular bleeding than depot leuprolide; conversely, depot leuprolide was associated with greater loss of bone density and a higher incidence of vasomotor symptoms. Weight gain was in the range of 0.6 kg in both groups.

Of note, DPMA is much less expensive than depot leuprolide.

Another study showed that increasing the dosage of DMPA did not improve efficacy over the standard dosage¹¹: DMPA, 150 mg IM, monthly, and DMPA, 150 mg IM, every 3 months produced similar relief of pelvic pain.

Oral medroxyprogesterone acetate, prescribed at high dosages, is also effective for pelvic pain caused by endometriosis. In a pilot study (n=21), oral MPA, 50 mg/d for 4 months, alleviated dysmenorrhea, dyspareunia, pelvic pain, dyschezia, and pelvic tenderness and decreased pelvic nodularity. Sixty percent of subjects reported weight gain— 1.5 kg, on average.¹²

Progestin-releasing devices: Mirena and Implanon

Many pilot studies have reported that the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for pelvic pain caused by endometriosis.^13-17 For example:

Research. In a small clinical trial, 30 women who had pelvic pain and endometriosis were randomized to receive an LNG-IUS (Mirena) or DMPA, 150 mg IM, every 3 months for 3 years.¹³ Both therapies were effective at reducing pelvic pain.

At the conclusion of the study, more women opted to retain the LNG-IUS (87%) than to continue DMPA injection (47%). Bone density was maintained in women who had the LNG-IUS placed but slightly diminished in women receiving DMPA.

In a pilot study of an etonogestrel releasing implant (Implanon), 41 women who had pelvic pain and endometriosis were randomized to receive the implant or DMPA, 150 mg IM, every 3 months for 1 year.¹⁸ Both therapies were similarly effective at reducing pelvic pain.

Notably, irregular uterine bleeding is a common problem when the etonogestrel-releasing implant is used to treat endometriosis. Achieving amenorrhea or oligomenorrhea is an important goal for women who suffer from pelvic pain caused by endometriosis.

My recommendation

Most ObGyns see patients who are suffering from difficult-to-treat pelvic pain caused by endometriosis. Many of these patients have not had a trial of a progestin, such as NEA, DMPA, or the LNG-IUS that I use in my practice.

Progestins are, as I’ve described, effective for pelvic pain. They are also relatively inexpensive and have a side-effect profile that most patients find acceptable. I recommend that you try a progestin for your patients who have refractory pelvic pain.

CASE

Your patient is a 26-year-old G0 woman who has a long history of progressively worsening dysmenorrhea, pelvic pain, and dyspareunia. In the recent past, she was treated with nonsteroidal anti-inflammatory drugs, a cyclic estrogen-progestin contraceptive, and a continuous estrogen-progestin contraceptive—in that order, and without appreciable relief of the pain.

Recently, the woman underwent laparoscopy, which demonstrated Stage-II endometriosis, which was ablated.

What would you prescribe for her postoperatively to alleviate symptoms?

Endometriosis will be diagnosed in approximately 8% of women of reproductive age.¹ Pelvic pain, dysmenorrhea, and deep dyspareunia are common symptoms of endometriosis that interfere with quality of life.

Endometriosis is a chronic disease best managed by developing a life-long treatment plan. Following laparoscopic diagnosis and treatment, many experts strongly recommend postoperative hormone-suppressive therapy to reduce the risk that severe pelvic pain will recur, requiring re-operation.

Options for postoperative hormonal treatment of endometriosis include:

• an estrogen–progestin contraceptive
• a progestin (norethindrone acetate [NEA]; depot medroxyprogesterone acetate [DMPA]; oral medroxyprogesterone acetate; the levonorgestrel-releasing intrauterine system [LNG-IUS; Mirena]; and the progestin-releasing implant [Implanon])
• a gonadotropin-releasing hormone (GnRH) agonist (depot leuprolide [Depot Lupron]; nafarelin nasal spray [Synarel]).

CASE Continued

Considering that both cyclic and continuous estrogen-progestin contraceptives have already failed to provide adequate pain relief for your patient, you know that you should offer an alternative to her. Taking into account that progestins are significantly less costly than a GnRH agonist, a progestin formulation might, for her, be considered a first-line postoperative treatment of symptoms of endometriosis.

Options when considering a progestin

Norethindrone acetate

This agent is available in a single formulation: a 5-mg tablet; however, dosages ranging from 2.5 mg/d (half of a tablet) to 15 mg/d have been reported to be effective for relieving pain caused by endometriosis.

What is it? NEA is an androgenic progestin that suppresses luteinizing hormone and follicle-stimulating hormone, thus reducing production of ovarian estrogen. In the absence of ovarian estrogen, endometriosis lesions atrophy. In addition, NEA binds to, and stimulates, endometrial progestin and androgen receptors, resulting in decidualization and atrophy of both eutopic and ectopic endometrial tissue.

Importantly, NEA does not appear to cause bone loss, a phenomenon that is common with agents such as the GnRH agonists or DPMA.^2-4

The research record. One randomized study, two pilot studies, and one large observational study have reported that NEA is effective for pelvic pain caused by endometriosis.

In the randomized trial, 90 women who had moderate or severe pelvic pain and rectovaginal endometriosis, and who remained symptomatic after conservative surgery, were randomized to receive NEA, 2.5 mg/d, or a low-dose estrogen-progestin contraceptive (ethinyl estradiol, 10 μg, plus cyproterone acetate, 3 mg) daily for 12 months.⁵ Both treatment groups reported significant and similar decreases in dysmenorrhea, deep dyspareunia, non-menstrual pain and dyschezia.

In a small pilot study, 40 women who had pelvic pain and colorectal endometriosis were treated with NEA 2.5 mg/d for 12 months. The drug produced significant improvement in dysmenorrhea, pelvic pain, deep dyspareunia, dyschezia, and cyclic rectal bleeding.⁶

In another pilot study, women who had pelvic pain and rectovaginal endometriosis were treated with either an aromatase inhibitor (letrozole, 2.5 mg/d) plus NEA (2.5 mg/d) or NEA (2.5 mg/d) alone for 6 months. Both treatments resulted in a significant improvement in pelvic pain and deep dyspareunia. Improvement in pain scores was greater with letrozole plus NEA; patients were more satisfied with NEA monotherapy than with the combined letrozole-NEA treatment, however, because the former was associated with fewer side effects.⁷

In a large (n=194) observational study of the postoperative use of NEA in young women with pelvic pain and endometriosis, NEA at dosages as high as 15 mg/d significantly diminished pelvic pain and self-reported menstrual bleeding. All subjects were started on a dosage of 5 mg/d, which was increased in 2.5-mg increments every 2 weeks to achieve the goals of amenorrhea and a lessening of pelvic pain; the maximum dosage administered was 15 mg/d. Mean duration of NEA use was 13 months; 75% of subjects took the maximum prescribed dosage of 15 mg at some point during treatment. The most commonly reported side effects were weight gain (16% of women); acne (10%); mood lability (9%); and vasomotor symptoms (8%).⁸

In summary. NEA is effective for treating pelvic pain caused by endometriosis at dosages from 2.5 mg/d to 15 mg/d. An important goal of treatment is a decrease in pain symptoms and amenorrhea; a dosage of 2.5 mg is often insufficient to reliably achieve both of those objectives.

In my practice I begin therapy at a dosage of 5 mg/d; the drug is effective for most patients at that dosage. If 5 mg/d does not reduce pain, I increase the dosage by 2.5 mg (half of a tablet) daily every 4 weeks, to a maximum dosage of 10 mg/d (two tablets). If that dosage is ineffective, I usually discontinue NEA and switch to a GnRH agonist.

Depot medroxyprogesterone acetate; oral medroxy-progesterone acetate

DMPA is available in two FDA-approved formulations:

• a 150-mg dose given by intramuscular injection every 3 months
• a 104-mg dose given by subcutaneous injection every 3 months.

Research. The results of two large clinical trials, comprising a total of more than 550 subjects, showed that DMPA (104 mg, SC, every 3 months) and depot leuprolide (11.25 mg, IM, every 3 months or 3.75 mg, monthly) were each equally effective in relieving dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and pelvic induration in women who had endometriosis.^9,10

DMPA was associated with a greater rate of episodes of irregular bleeding than depot leuprolide; conversely, depot leuprolide was associated with greater loss of bone density and a higher incidence of vasomotor symptoms. Weight gain was in the range of 0.6 kg in both groups.

Of note, DPMA is much less expensive than depot leuprolide.

Another study showed that increasing the dosage of DMPA did not improve efficacy over the standard dosage¹¹: DMPA, 150 mg IM, monthly, and DMPA, 150 mg IM, every 3 months produced similar relief of pelvic pain.

Oral medroxyprogesterone acetate, prescribed at high dosages, is also effective for pelvic pain caused by endometriosis. In a pilot study (n=21), oral MPA, 50 mg/d for 4 months, alleviated dysmenorrhea, dyspareunia, pelvic pain, dyschezia, and pelvic tenderness and decreased pelvic nodularity. Sixty percent of subjects reported weight gain— 1.5 kg, on average.¹²

Progestin-releasing devices: Mirena and Implanon

Many pilot studies have reported that the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for pelvic pain caused by endometriosis.^13-17 For example:

Research. In a small clinical trial, 30 women who had pelvic pain and endometriosis were randomized to receive an LNG-IUS (Mirena) or DMPA, 150 mg IM, every 3 months for 3 years.¹³ Both therapies were effective at reducing pelvic pain.

At the conclusion of the study, more women opted to retain the LNG-IUS (87%) than to continue DMPA injection (47%). Bone density was maintained in women who had the LNG-IUS placed but slightly diminished in women receiving DMPA.

In a pilot study of an etonogestrel releasing implant (Implanon), 41 women who had pelvic pain and endometriosis were randomized to receive the implant or DMPA, 150 mg IM, every 3 months for 1 year.¹⁸ Both therapies were similarly effective at reducing pelvic pain.

Notably, irregular uterine bleeding is a common problem when the etonogestrel-releasing implant is used to treat endometriosis. Achieving amenorrhea or oligomenorrhea is an important goal for women who suffer from pelvic pain caused by endometriosis.

My recommendation

Most ObGyns see patients who are suffering from difficult-to-treat pelvic pain caused by endometriosis. Many of these patients have not had a trial of a progestin, such as NEA, DMPA, or the LNG-IUS that I use in my practice.

Progestins are, as I’ve described, effective for pelvic pain. They are also relatively inexpensive and have a side-effect profile that most patients find acceptable. I recommend that you try a progestin for your patients who have refractory pelvic pain.

CASE

Your patient is a 26-year-old G0 woman who has a long history of progressively worsening dysmenorrhea, pelvic pain, and dyspareunia. In the recent past, she was treated with nonsteroidal anti-inflammatory drugs, a cyclic estrogen-progestin contraceptive, and a continuous estrogen-progestin contraceptive—in that order, and without appreciable relief of the pain.

Recently, the woman underwent laparoscopy, which demonstrated Stage-II endometriosis, which was ablated.

What would you prescribe for her postoperatively to alleviate symptoms?

Endometriosis will be diagnosed in approximately 8% of women of reproductive age.¹ Pelvic pain, dysmenorrhea, and deep dyspareunia are common symptoms of endometriosis that interfere with quality of life.

Endometriosis is a chronic disease best managed by developing a life-long treatment plan. Following laparoscopic diagnosis and treatment, many experts strongly recommend postoperative hormone-suppressive therapy to reduce the risk that severe pelvic pain will recur, requiring re-operation.

Options for postoperative hormonal treatment of endometriosis include:

• an estrogen–progestin contraceptive
• a progestin (norethindrone acetate [NEA]; depot medroxyprogesterone acetate [DMPA]; oral medroxyprogesterone acetate; the levonorgestrel-releasing intrauterine system [LNG-IUS; Mirena]; and the progestin-releasing implant [Implanon])
• a gonadotropin-releasing hormone (GnRH) agonist (depot leuprolide [Depot Lupron]; nafarelin nasal spray [Synarel]).

CASE Continued

Considering that both cyclic and continuous estrogen-progestin contraceptives have already failed to provide adequate pain relief for your patient, you know that you should offer an alternative to her. Taking into account that progestins are significantly less costly than a GnRH agonist, a progestin formulation might, for her, be considered a first-line postoperative treatment of symptoms of endometriosis.

Options when considering a progestin

Norethindrone acetate

This agent is available in a single formulation: a 5-mg tablet; however, dosages ranging from 2.5 mg/d (half of a tablet) to 15 mg/d have been reported to be effective for relieving pain caused by endometriosis.

What is it? NEA is an androgenic progestin that suppresses luteinizing hormone and follicle-stimulating hormone, thus reducing production of ovarian estrogen. In the absence of ovarian estrogen, endometriosis lesions atrophy. In addition, NEA binds to, and stimulates, endometrial progestin and androgen receptors, resulting in decidualization and atrophy of both eutopic and ectopic endometrial tissue.

Importantly, NEA does not appear to cause bone loss, a phenomenon that is common with agents such as the GnRH agonists or DPMA.^2-4

The research record. One randomized study, two pilot studies, and one large observational study have reported that NEA is effective for pelvic pain caused by endometriosis.

In the randomized trial, 90 women who had moderate or severe pelvic pain and rectovaginal endometriosis, and who remained symptomatic after conservative surgery, were randomized to receive NEA, 2.5 mg/d, or a low-dose estrogen-progestin contraceptive (ethinyl estradiol, 10 μg, plus cyproterone acetate, 3 mg) daily for 12 months.⁵ Both treatment groups reported significant and similar decreases in dysmenorrhea, deep dyspareunia, non-menstrual pain and dyschezia.

In a small pilot study, 40 women who had pelvic pain and colorectal endometriosis were treated with NEA 2.5 mg/d for 12 months. The drug produced significant improvement in dysmenorrhea, pelvic pain, deep dyspareunia, dyschezia, and cyclic rectal bleeding.⁶

In another pilot study, women who had pelvic pain and rectovaginal endometriosis were treated with either an aromatase inhibitor (letrozole, 2.5 mg/d) plus NEA (2.5 mg/d) or NEA (2.5 mg/d) alone for 6 months. Both treatments resulted in a significant improvement in pelvic pain and deep dyspareunia. Improvement in pain scores was greater with letrozole plus NEA; patients were more satisfied with NEA monotherapy than with the combined letrozole-NEA treatment, however, because the former was associated with fewer side effects.⁷

In a large (n=194) observational study of the postoperative use of NEA in young women with pelvic pain and endometriosis, NEA at dosages as high as 15 mg/d significantly diminished pelvic pain and self-reported menstrual bleeding. All subjects were started on a dosage of 5 mg/d, which was increased in 2.5-mg increments every 2 weeks to achieve the goals of amenorrhea and a lessening of pelvic pain; the maximum dosage administered was 15 mg/d. Mean duration of NEA use was 13 months; 75% of subjects took the maximum prescribed dosage of 15 mg at some point during treatment. The most commonly reported side effects were weight gain (16% of women); acne (10%); mood lability (9%); and vasomotor symptoms (8%).⁸

In summary. NEA is effective for treating pelvic pain caused by endometriosis at dosages from 2.5 mg/d to 15 mg/d. An important goal of treatment is a decrease in pain symptoms and amenorrhea; a dosage of 2.5 mg is often insufficient to reliably achieve both of those objectives.

In my practice I begin therapy at a dosage of 5 mg/d; the drug is effective for most patients at that dosage. If 5 mg/d does not reduce pain, I increase the dosage by 2.5 mg (half of a tablet) daily every 4 weeks, to a maximum dosage of 10 mg/d (two tablets). If that dosage is ineffective, I usually discontinue NEA and switch to a GnRH agonist.

Depot medroxyprogesterone acetate; oral medroxy-progesterone acetate

DMPA is available in two FDA-approved formulations:

• a 150-mg dose given by intramuscular injection every 3 months
• a 104-mg dose given by subcutaneous injection every 3 months.

Research. The results of two large clinical trials, comprising a total of more than 550 subjects, showed that DMPA (104 mg, SC, every 3 months) and depot leuprolide (11.25 mg, IM, every 3 months or 3.75 mg, monthly) were each equally effective in relieving dysmenorrhea, dyspareunia, pelvic pain, pelvic tenderness, and pelvic induration in women who had endometriosis.^9,10

DMPA was associated with a greater rate of episodes of irregular bleeding than depot leuprolide; conversely, depot leuprolide was associated with greater loss of bone density and a higher incidence of vasomotor symptoms. Weight gain was in the range of 0.6 kg in both groups.

Of note, DPMA is much less expensive than depot leuprolide.

Another study showed that increasing the dosage of DMPA did not improve efficacy over the standard dosage¹¹: DMPA, 150 mg IM, monthly, and DMPA, 150 mg IM, every 3 months produced similar relief of pelvic pain.

Oral medroxyprogesterone acetate, prescribed at high dosages, is also effective for pelvic pain caused by endometriosis. In a pilot study (n=21), oral MPA, 50 mg/d for 4 months, alleviated dysmenorrhea, dyspareunia, pelvic pain, dyschezia, and pelvic tenderness and decreased pelvic nodularity. Sixty percent of subjects reported weight gain— 1.5 kg, on average.¹²

Progestin-releasing devices: Mirena and Implanon

Many pilot studies have reported that the levonorgestrel-releasing intrauterine system (LNG-IUS) is effective for pelvic pain caused by endometriosis.^13-17 For example:

Research. In a small clinical trial, 30 women who had pelvic pain and endometriosis were randomized to receive an LNG-IUS (Mirena) or DMPA, 150 mg IM, every 3 months for 3 years.¹³ Both therapies were effective at reducing pelvic pain.

At the conclusion of the study, more women opted to retain the LNG-IUS (87%) than to continue DMPA injection (47%). Bone density was maintained in women who had the LNG-IUS placed but slightly diminished in women receiving DMPA.

In a pilot study of an etonogestrel releasing implant (Implanon), 41 women who had pelvic pain and endometriosis were randomized to receive the implant or DMPA, 150 mg IM, every 3 months for 1 year.¹⁸ Both therapies were similarly effective at reducing pelvic pain.

Notably, irregular uterine bleeding is a common problem when the etonogestrel-releasing implant is used to treat endometriosis. Achieving amenorrhea or oligomenorrhea is an important goal for women who suffer from pelvic pain caused by endometriosis.

My recommendation

Most ObGyns see patients who are suffering from difficult-to-treat pelvic pain caused by endometriosis. Many of these patients have not had a trial of a progestin, such as NEA, DMPA, or the LNG-IUS that I use in my practice.

Progestins are, as I’ve described, effective for pelvic pain. They are also relatively inexpensive and have a side-effect profile that most patients find acceptable. I recommend that you try a progestin for your patients who have refractory pelvic pain.

Who is a survivor? Am I a survivor? Are you a survivor? What does a survivor need? How can community oncologists help? These are among the many questions a community oncologist can expect to hear during the course of treating a cancer patient, from the diagnosis, through the decisions about therapy, at all stages of treatment, and well into aftercare and follow-up. A “patient” used to be someone in active treatment, and a “survivor” was someone who had been free of disease for 5 years. More recently, Ellen Stoval of the National Coalition for Cancer Survivorship noted that the term “cancer survivor” can be used “to describe anyone who has been diagnosed with cancer as well as caregivers and loved ones of those diagnosed with the disease.”1 Her broader perspective more accurately captures the multifaceted nature of survivorship...

*For a PDF of the full article, click on the link to the left of this introduction.

Who is a survivor? Am I a survivor? Are you a survivor? What does a survivor need? How can community oncologists help? These are among the many questions a community oncologist can expect to hear during the course of treating a cancer patient, from the diagnosis, through the decisions about therapy, at all stages of treatment, and well into aftercare and follow-up. A “patient” used to be someone in active treatment, and a “survivor” was someone who had been free of disease for 5 years. More recently, Ellen Stoval of the National Coalition for Cancer Survivorship noted that the term “cancer survivor” can be used “to describe anyone who has been diagnosed with cancer as well as caregivers and loved ones of those diagnosed with the disease.”1 Her broader perspective more accurately captures the multifaceted nature of survivorship...

*For a PDF of the full article, click on the link to the left of this introduction.

Who is a survivor? Am I a survivor? Are you a survivor? What does a survivor need? How can community oncologists help? These are among the many questions a community oncologist can expect to hear during the course of treating a cancer patient, from the diagnosis, through the decisions about therapy, at all stages of treatment, and well into aftercare and follow-up. A “patient” used to be someone in active treatment, and a “survivor” was someone who had been free of disease for 5 years. More recently, Ellen Stoval of the National Coalition for Cancer Survivorship noted that the term “cancer survivor” can be used “to describe anyone who has been diagnosed with cancer as well as caregivers and loved ones of those diagnosed with the disease.”1 Her broader perspective more accurately captures the multifaceted nature of survivorship...

*For a PDF of the full article, click on the link to the left of this introduction.

With the introduction of tyrosine kinase inhibitor (TKI) therapy and the development of more sensitive monitoring techniques, the management of patients with chronic myeloid leukemia (CML) has evolved considerably over the last decade. In this review, we summarize the available literature evaluating the safety and efficacy of the TKIs imatinib, dasatinib, and nilotinib for information relevant to patient management to provide insight into long-term management of CML patients who receive TKI therapy. We suggest that these developments in treatment have expanded the role of oncology nurses, who can help address new issues that have arisen for patients learning to adapt to a chronic condition. The essential practice of monitoring, the critical importance of medication adherence, the safety profile of the three available TKIs, strategies for supportive care related to adverse events, drugdrug and drug-food interactions, and family planning are important aspects of long-term patient management...

 *For a PDF of the full article, click on the link to the left of this introduction.

With the introduction of tyrosine kinase inhibitor (TKI) therapy and the development of more sensitive monitoring techniques, the management of patients with chronic myeloid leukemia (CML) has evolved considerably over the last decade. In this review, we summarize the available literature evaluating the safety and efficacy of the TKIs imatinib, dasatinib, and nilotinib for information relevant to patient management to provide insight into long-term management of CML patients who receive TKI therapy. We suggest that these developments in treatment have expanded the role of oncology nurses, who can help address new issues that have arisen for patients learning to adapt to a chronic condition. The essential practice of monitoring, the critical importance of medication adherence, the safety profile of the three available TKIs, strategies for supportive care related to adverse events, drugdrug and drug-food interactions, and family planning are important aspects of long-term patient management...

 *For a PDF of the full article, click on the link to the left of this introduction.

With the introduction of tyrosine kinase inhibitor (TKI) therapy and the development of more sensitive monitoring techniques, the management of patients with chronic myeloid leukemia (CML) has evolved considerably over the last decade. In this review, we summarize the available literature evaluating the safety and efficacy of the TKIs imatinib, dasatinib, and nilotinib for information relevant to patient management to provide insight into long-term management of CML patients who receive TKI therapy. We suggest that these developments in treatment have expanded the role of oncology nurses, who can help address new issues that have arisen for patients learning to adapt to a chronic condition. The essential practice of monitoring, the critical importance of medication adherence, the safety profile of the three available TKIs, strategies for supportive care related to adverse events, drugdrug and drug-food interactions, and family planning are important aspects of long-term patient management...

 *For a PDF of the full article, click on the link to the left of this introduction.

Renal cell carcinoma (RCC) continues to exert a substantial disease burden. Increasing knowledge of the molecular signaling pathways associated with renal cancer has led to the development of targeted therapies for advanced RCC, including several antiangiogenic agents designed to inhibit development of abnormal blood vessels that sustain tumor growth. Axitinib is an investigational antiangiogenic agent that targets vascular endothelial growth factor receptors 1, 2, and 3. In phase II studies, axitinib elicited significant response rates in patients with advanced RCC refractory to cytokines or sorafenib. In a phase III study of axitinib versus sorafenib in patients with metastatic RCC, axitinib demonstrated clinically significant improvement in progression-free survival compared with sorafenib. As with other targeted agents, side effects associated with axitinib, such as hypertension, fatigue, and diarrhea, can negatively affect the patient’s physical and emotional states and quality of life, thus jeopardizing adherence to and the effectiveness of the treatment plan. Clinicians should be aware of side effects that may occur during treatment and manage them proactively. Nurses should educate patients about possible side effects and their management before axitinib treatment is initiated. Management strategies include early reporting of the symptoms, regular clinic visits and laboratory tests, ongoing review of concomitant medications, and prompt treatment of side effects and follow-up to assess the effectiveness of interventions, which could include treatment interruption and/or dose reduction. These approaches would help maximize the patient adherence to therapy, quality of life, and clinical outcomes.

 *For a PDF of the full article, click on the link to the left of this introduction.

Renal cell carcinoma (RCC) continues to exert a substantial disease burden. Increasing knowledge of the molecular signaling pathways associated with renal cancer has led to the development of targeted therapies for advanced RCC, including several antiangiogenic agents designed to inhibit development of abnormal blood vessels that sustain tumor growth. Axitinib is an investigational antiangiogenic agent that targets vascular endothelial growth factor receptors 1, 2, and 3. In phase II studies, axitinib elicited significant response rates in patients with advanced RCC refractory to cytokines or sorafenib. In a phase III study of axitinib versus sorafenib in patients with metastatic RCC, axitinib demonstrated clinically significant improvement in progression-free survival compared with sorafenib. As with other targeted agents, side effects associated with axitinib, such as hypertension, fatigue, and diarrhea, can negatively affect the patient’s physical and emotional states and quality of life, thus jeopardizing adherence to and the effectiveness of the treatment plan. Clinicians should be aware of side effects that may occur during treatment and manage them proactively. Nurses should educate patients about possible side effects and their management before axitinib treatment is initiated. Management strategies include early reporting of the symptoms, regular clinic visits and laboratory tests, ongoing review of concomitant medications, and prompt treatment of side effects and follow-up to assess the effectiveness of interventions, which could include treatment interruption and/or dose reduction. These approaches would help maximize the patient adherence to therapy, quality of life, and clinical outcomes.

 *For a PDF of the full article, click on the link to the left of this introduction.

Renal cell carcinoma (RCC) continues to exert a substantial disease burden. Increasing knowledge of the molecular signaling pathways associated with renal cancer has led to the development of targeted therapies for advanced RCC, including several antiangiogenic agents designed to inhibit development of abnormal blood vessels that sustain tumor growth. Axitinib is an investigational antiangiogenic agent that targets vascular endothelial growth factor receptors 1, 2, and 3. In phase II studies, axitinib elicited significant response rates in patients with advanced RCC refractory to cytokines or sorafenib. In a phase III study of axitinib versus sorafenib in patients with metastatic RCC, axitinib demonstrated clinically significant improvement in progression-free survival compared with sorafenib. As with other targeted agents, side effects associated with axitinib, such as hypertension, fatigue, and diarrhea, can negatively affect the patient’s physical and emotional states and quality of life, thus jeopardizing adherence to and the effectiveness of the treatment plan. Clinicians should be aware of side effects that may occur during treatment and manage them proactively. Nurses should educate patients about possible side effects and their management before axitinib treatment is initiated. Management strategies include early reporting of the symptoms, regular clinic visits and laboratory tests, ongoing review of concomitant medications, and prompt treatment of side effects and follow-up to assess the effectiveness of interventions, which could include treatment interruption and/or dose reduction. These approaches would help maximize the patient adherence to therapy, quality of life, and clinical outcomes.

 *For a PDF of the full article, click on the link to the left of this introduction.

Residents and attendings have divergent attitudes toward smartphone use during inpatient attending rounds, according to a researcher studying the topic.

Rachel Katz-Sidlow, MD, department of pediatrics, Jacobi Medical Center, Bronx, N.Y., is looking into the potential disadvantages of the phones if users are sending or receiving texts, emails, or pictures during rounds. Her preliminary research shows that a majority of faculty members believe a policy should be put in place to codify smartphone use.

“I truly think that policies to regulate smartphone use during patient management sessions are necessary, and will become commonplace in the near future until there are technology-driven solutions put into place,” says Dr. Katz-Sidlow.

Her research, currently in peer review for publication in the Journal of Hospital Medicine, comes as the ubiquity of smartphone technology has begun to be questioned by observers in the mainstream media. She says the majority of attendings and residents who responded to her initial questioning agree that smartphones “can be a serious source of distraction” during rounds.

The policy Dr. Katz-Sidlow is testing at Jacobi Medical Center defines a “smartphone” as any personal mobile communication device, including basic cellphones, Internet-enabled cellphones, and tablet computers. The beta policy restricts smartphone use during rounds to patient-care tasks, and would require all team members’ devices to be silenced or turned off at the beginning of rounds.

“Smartphones are here to stay and will become even more common in the future,” says Dr. Katz-Sidlow. “They’re such a valuable tool in medical education and patient care ... but there needs to be balance.”

Residents and attendings have divergent attitudes toward smartphone use during inpatient attending rounds, according to a researcher studying the topic.

Rachel Katz-Sidlow, MD, department of pediatrics, Jacobi Medical Center, Bronx, N.Y., is looking into the potential disadvantages of the phones if users are sending or receiving texts, emails, or pictures during rounds. Her preliminary research shows that a majority of faculty members believe a policy should be put in place to codify smartphone use.

“I truly think that policies to regulate smartphone use during patient management sessions are necessary, and will become commonplace in the near future until there are technology-driven solutions put into place,” says Dr. Katz-Sidlow.

Her research, currently in peer review for publication in the Journal of Hospital Medicine, comes as the ubiquity of smartphone technology has begun to be questioned by observers in the mainstream media. She says the majority of attendings and residents who responded to her initial questioning agree that smartphones “can be a serious source of distraction” during rounds.

The policy Dr. Katz-Sidlow is testing at Jacobi Medical Center defines a “smartphone” as any personal mobile communication device, including basic cellphones, Internet-enabled cellphones, and tablet computers. The beta policy restricts smartphone use during rounds to patient-care tasks, and would require all team members’ devices to be silenced or turned off at the beginning of rounds.

“Smartphones are here to stay and will become even more common in the future,” says Dr. Katz-Sidlow. “They’re such a valuable tool in medical education and patient care ... but there needs to be balance.”

Residents and attendings have divergent attitudes toward smartphone use during inpatient attending rounds, according to a researcher studying the topic.

Rachel Katz-Sidlow, MD, department of pediatrics, Jacobi Medical Center, Bronx, N.Y., is looking into the potential disadvantages of the phones if users are sending or receiving texts, emails, or pictures during rounds. Her preliminary research shows that a majority of faculty members believe a policy should be put in place to codify smartphone use.

“I truly think that policies to regulate smartphone use during patient management sessions are necessary, and will become commonplace in the near future until there are technology-driven solutions put into place,” says Dr. Katz-Sidlow.

Her research, currently in peer review for publication in the Journal of Hospital Medicine, comes as the ubiquity of smartphone technology has begun to be questioned by observers in the mainstream media. She says the majority of attendings and residents who responded to her initial questioning agree that smartphones “can be a serious source of distraction” during rounds.

The policy Dr. Katz-Sidlow is testing at Jacobi Medical Center defines a “smartphone” as any personal mobile communication device, including basic cellphones, Internet-enabled cellphones, and tablet computers. The beta policy restricts smartphone use during rounds to patient-care tasks, and would require all team members’ devices to be silenced or turned off at the beginning of rounds.

“Smartphones are here to stay and will become even more common in the future,” says Dr. Katz-Sidlow. “They’re such a valuable tool in medical education and patient care ... but there needs to be balance.”

A poster presented at the Center to Advance Palliative Care national seminar in San Diego in November described a growing collaboration between the HM service and the palliative-care team at a Wisconsin medical center as part of efforts to control readmissions using tools from SHM’s Project BOOST (Better Outcomes for Older Adults through Safe Transitions).

On admission to 227-bed Aurora West Allis (Wis.) Medical Center, all patients assigned to a hospitalist are assessed for readmission risk factors. If a risk factor is identified, the hospital has established a set of specific interventions, including a palliative-care consultation.

“Basically, we took the BOOST tools and developed a physician action plan behind those risk factors,” says Andrew McDonagh, MD, head of the center’s hospitalist service.

Dr. McDonagh started Aurora West Allis’ HM service in 2008, and Timothy Jessick, DO, initiated the palliative-care service in 2010. “As our programs grew together, it became apparent that there were significant synergies between the two specialties, so we took the opportunity to work together in several ways,” Dr. McDonagh says.

A Palliative Care Quality Indicators Checklist, which looks for four key clinical indicators, triggers hospitalists and unit nurses to order the palliative consult. If an elderly patient has multiple admissions for the same diagnosis, the second admission triggers a geriatric consultation, and the third admission gets a palliative-care consult.

Hospitalists at the medical center are given education and modeling on how to hold family conferences with patients and their families to elicit their goals of care. Collaboration between HM and palliative care is spreading to the hospital’s ICUs, to patients transitioning out of the hospital to nursing homes, and to two other Aurora hospitals in the Milwaukee area, Dr. McDonagh explains. Since the BOOST tools have been implemented, preliminary evidence points to reduced readmissions, increased patient satisfaction, and increased palliative-care consults at the hospital.

“In the future, doing our job well as hospitalists will be more than just addressing medical needs but tailoring our care plans to the individual patient. Palliative care helps us better define appropriate care for these patients, looking beyond the trees for the forest,” he says. “I believe I’m a better clinician for being part of this relationship.”

A poster presented at the Center to Advance Palliative Care national seminar in San Diego in November described a growing collaboration between the HM service and the palliative-care team at a Wisconsin medical center as part of efforts to control readmissions using tools from SHM’s Project BOOST (Better Outcomes for Older Adults through Safe Transitions).

On admission to 227-bed Aurora West Allis (Wis.) Medical Center, all patients assigned to a hospitalist are assessed for readmission risk factors. If a risk factor is identified, the hospital has established a set of specific interventions, including a palliative-care consultation.

“Basically, we took the BOOST tools and developed a physician action plan behind those risk factors,” says Andrew McDonagh, MD, head of the center’s hospitalist service.

Dr. McDonagh started Aurora West Allis’ HM service in 2008, and Timothy Jessick, DO, initiated the palliative-care service in 2010. “As our programs grew together, it became apparent that there were significant synergies between the two specialties, so we took the opportunity to work together in several ways,” Dr. McDonagh says.

A Palliative Care Quality Indicators Checklist, which looks for four key clinical indicators, triggers hospitalists and unit nurses to order the palliative consult. If an elderly patient has multiple admissions for the same diagnosis, the second admission triggers a geriatric consultation, and the third admission gets a palliative-care consult.

Hospitalists at the medical center are given education and modeling on how to hold family conferences with patients and their families to elicit their goals of care. Collaboration between HM and palliative care is spreading to the hospital’s ICUs, to patients transitioning out of the hospital to nursing homes, and to two other Aurora hospitals in the Milwaukee area, Dr. McDonagh explains. Since the BOOST tools have been implemented, preliminary evidence points to reduced readmissions, increased patient satisfaction, and increased palliative-care consults at the hospital.

“In the future, doing our job well as hospitalists will be more than just addressing medical needs but tailoring our care plans to the individual patient. Palliative care helps us better define appropriate care for these patients, looking beyond the trees for the forest,” he says. “I believe I’m a better clinician for being part of this relationship.”

A poster presented at the Center to Advance Palliative Care national seminar in San Diego in November described a growing collaboration between the HM service and the palliative-care team at a Wisconsin medical center as part of efforts to control readmissions using tools from SHM’s Project BOOST (Better Outcomes for Older Adults through Safe Transitions).

On admission to 227-bed Aurora West Allis (Wis.) Medical Center, all patients assigned to a hospitalist are assessed for readmission risk factors. If a risk factor is identified, the hospital has established a set of specific interventions, including a palliative-care consultation.

“Basically, we took the BOOST tools and developed a physician action plan behind those risk factors,” says Andrew McDonagh, MD, head of the center’s hospitalist service.

Dr. McDonagh started Aurora West Allis’ HM service in 2008, and Timothy Jessick, DO, initiated the palliative-care service in 2010. “As our programs grew together, it became apparent that there were significant synergies between the two specialties, so we took the opportunity to work together in several ways,” Dr. McDonagh says.

A Palliative Care Quality Indicators Checklist, which looks for four key clinical indicators, triggers hospitalists and unit nurses to order the palliative consult. If an elderly patient has multiple admissions for the same diagnosis, the second admission triggers a geriatric consultation, and the third admission gets a palliative-care consult.

Hospitalists at the medical center are given education and modeling on how to hold family conferences with patients and their families to elicit their goals of care. Collaboration between HM and palliative care is spreading to the hospital’s ICUs, to patients transitioning out of the hospital to nursing homes, and to two other Aurora hospitals in the Milwaukee area, Dr. McDonagh explains. Since the BOOST tools have been implemented, preliminary evidence points to reduced readmissions, increased patient satisfaction, and increased palliative-care consults at the hospital.

“In the future, doing our job well as hospitalists will be more than just addressing medical needs but tailoring our care plans to the individual patient. Palliative care helps us better define appropriate care for these patients, looking beyond the trees for the forest,” he says. “I believe I’m a better clinician for being part of this relationship.”

The Food and Drug Administration on Jan. 30 approved a type 2 diabetes therapy that combines linagliptin and metformin in a single tablet taken twice daily.*

The approval was announced by Eli Lilly and Boehringer Ingelheim. The companies jointly developed the tablet, to be marketed as Jentadueto. Linagliptin is a dipeptidyl peptidase–4 (DPP-4) inhibitor that was approved for marketing in May 2011.

The linagliptin/metformin combination is intended to be used in conjunction with diet and exercise to improve glycemic control. Jentadueto was approved based on a 24-week, double-blind, placebo-controlled study that compared six arms: placebo, linagliptin once daily; 500 mg metformin twice daily; 2.5 mg linagliptin plus a 500-mg tablet of metformin twice daily; 1,000 mg metformin twice daily; and 2.5 mg linagliptin plus 1,000 mg metformin twice daily.

The actual combination tablet was not tested, but the FDA approved it based on bioequivalence studies, according to Lilly. The 2.5-mg linagliptin plus 1,000-mg metformin arm had the best results, reducing hemoglobin A_1c by up to 1.7%. The two tablets did not cause any meaningful changes in body weight, according to a company statement.

Lilly said that Jentadueto can be used alone or in combination with a sulfonylurea. It is not indicated for type 1 diabetes or diabetic ketoacidosis. Jentadueto has a boxed warning for the risk of lactic acidosis.

*Correction, 1/31/12: An earlier version of this story noted the incorrect approval date.

The Food and Drug Administration on Jan. 30 approved a type 2 diabetes therapy that combines linagliptin and metformin in a single tablet taken twice daily.*

The approval was announced by Eli Lilly and Boehringer Ingelheim. The companies jointly developed the tablet, to be marketed as Jentadueto. Linagliptin is a dipeptidyl peptidase–4 (DPP-4) inhibitor that was approved for marketing in May 2011.

The linagliptin/metformin combination is intended to be used in conjunction with diet and exercise to improve glycemic control. Jentadueto was approved based on a 24-week, double-blind, placebo-controlled study that compared six arms: placebo, linagliptin once daily; 500 mg metformin twice daily; 2.5 mg linagliptin plus a 500-mg tablet of metformin twice daily; 1,000 mg metformin twice daily; and 2.5 mg linagliptin plus 1,000 mg metformin twice daily.

The actual combination tablet was not tested, but the FDA approved it based on bioequivalence studies, according to Lilly. The 2.5-mg linagliptin plus 1,000-mg metformin arm had the best results, reducing hemoglobin A_1c by up to 1.7%. The two tablets did not cause any meaningful changes in body weight, according to a company statement.

Lilly said that Jentadueto can be used alone or in combination with a sulfonylurea. It is not indicated for type 1 diabetes or diabetic ketoacidosis. Jentadueto has a boxed warning for the risk of lactic acidosis.

*Correction, 1/31/12: An earlier version of this story noted the incorrect approval date.

The Food and Drug Administration on Jan. 30 approved a type 2 diabetes therapy that combines linagliptin and metformin in a single tablet taken twice daily.*

The approval was announced by Eli Lilly and Boehringer Ingelheim. The companies jointly developed the tablet, to be marketed as Jentadueto. Linagliptin is a dipeptidyl peptidase–4 (DPP-4) inhibitor that was approved for marketing in May 2011.

The linagliptin/metformin combination is intended to be used in conjunction with diet and exercise to improve glycemic control. Jentadueto was approved based on a 24-week, double-blind, placebo-controlled study that compared six arms: placebo, linagliptin once daily; 500 mg metformin twice daily; 2.5 mg linagliptin plus a 500-mg tablet of metformin twice daily; 1,000 mg metformin twice daily; and 2.5 mg linagliptin plus 1,000 mg metformin twice daily.

The actual combination tablet was not tested, but the FDA approved it based on bioequivalence studies, according to Lilly. The 2.5-mg linagliptin plus 1,000-mg metformin arm had the best results, reducing hemoglobin A_1c by up to 1.7%. The two tablets did not cause any meaningful changes in body weight, according to a company statement.

Lilly said that Jentadueto can be used alone or in combination with a sulfonylurea. It is not indicated for type 1 diabetes or diabetic ketoacidosis. Jentadueto has a boxed warning for the risk of lactic acidosis.

*Correction, 1/31/12: An earlier version of this story noted the incorrect approval date.

For pediatric burn patients, the percentage of total body surface area affected remains the strongest predictor of survival, according to a report published online Jan. 31 in the Lancet.

"We have established that, in a modern pediatric burn care setting, a burn size of roughly 60% total body surface area is a crucial threshold for postburn morbidity and mortality," wrote Dr. Robert Kraft of Shriners Hospitals for Children, Galveston, Texas, and his associates.

For decades, burn size has been the main prognostic factor for both adults and children with burn injuries. But recent improvements in burn care – including novel drug treatments, new grafting techniques and materials, and improved life-support systems and monitoring methods – have dramatically improved survival, according to the investigators. Because treatment decisions, including whether to transfer a patient to a specialized burn center, are based on the probability of survival, it was important to determine whether burn size was still predictive of major complications and mortality under current treatment conditions.

To do so, Dr. Kraft and his colleagues examined outcomes in all 952 patients admitted over a 1-year period to Galveston’s Shriners Hospital with burns involving 30% or more of their total body surface area. Most of the study patients were burned on 40%-49% of their bodies.

Burn size proved to be the strongest predictor of survival, with mortality rising significantly as burn size increased. "In patient groups with burns smaller than 60% total body surface area, there were only minor increases in mortality starting at 3% and reaching up to 7%," the investigators wrote.

A large increase in mortality was noted when burn size reached 62% of the total body surface area. Such patients had a tenfold higher risk of death, compared with those who had smaller burns, the investigators reported (Lancet 2012 [doi:10.1016/S0140-6736(11)61345-7]).

Large burns also were associated with significant increases in multiorgan failure, infection during ICU stay, and the need for more surgeries to excise tissue. The rate of multiorgan failure was 6%-12% and the rate of sepsis was only 2%-6% for burns involving up to 59% of the body surface area. These rates ballooned as high as 27%-45% for multiorgan failure and 15%-26% for sepsis when burns involved 60% or more of the body surface area.

In addition, blood glucose and insulin levels rose significantly with burns involving 60% or more of the total body surface area, as did resting energy expenditure. Together with concomitant changes in liver structure and function, these findings reflect a massive hypermetabolic response to burn injury, Dr. Kraft and his associates reported.

Cytokine levels also differed by size of burn. With burns involving 60% or more of the body surface area, the levels of interleukin-6, -8, -10, and -13; macrophage inflammatory protein 1beta; tumor necrosis factor–alpha; granulocyte colony-stimulating factor; interferon-gamma; granulocyte-macrophage colony stimulating factor; and C-reactive protein rose substantially for an extended period of time.

Given these findings, "we recommend that pediatric patients with greater than 60% total body surface area burns be immediately transferred to a specialized burn center. Furthermore, at the burn center, patients should be treated with increased vigilance and improved therapies, in view of the increased risk of poor outcome associated with this burn size," the researchers wrote.

After burn size, the presence of inhalation injury in addition to external burn injury was a significant predictor of mortality. Patients who sustained inhalation injury had a threefold higher risk of death than did patients with no inhalation injuries. "We recommend that the treating physician [keep] in mind that the presence of inhalation injury significantly affects postburn outcomes," they noted.

Patient age and sex showed no association with survival, and neither did the time interval between sustaining the burn and presenting for admission.

It was noteworthy that mortality rates in this study were relatively low, even among patients who had the most extensive burns. "In our opinion, [high survival was] attributable to an improved and aggressive treatment regimen," they added.

This study was supported by Shriners Hospitals for Children, the National Institutes of Health, the National Institute on Disability and Rehabilitation Research, the Institute for Translational Sciences, the CFI Leaders Opportunity fund, and Physicians’ Services Incorporated Foundation. The investigators reported having no financial conflicts of interest.

For pediatric burn patients, the percentage of total body surface area affected remains the strongest predictor of survival, according to a report published online Jan. 31 in the Lancet.

"We have established that, in a modern pediatric burn care setting, a burn size of roughly 60% total body surface area is a crucial threshold for postburn morbidity and mortality," wrote Dr. Robert Kraft of Shriners Hospitals for Children, Galveston, Texas, and his associates.

For decades, burn size has been the main prognostic factor for both adults and children with burn injuries. But recent improvements in burn care – including novel drug treatments, new grafting techniques and materials, and improved life-support systems and monitoring methods – have dramatically improved survival, according to the investigators. Because treatment decisions, including whether to transfer a patient to a specialized burn center, are based on the probability of survival, it was important to determine whether burn size was still predictive of major complications and mortality under current treatment conditions.

To do so, Dr. Kraft and his colleagues examined outcomes in all 952 patients admitted over a 1-year period to Galveston’s Shriners Hospital with burns involving 30% or more of their total body surface area. Most of the study patients were burned on 40%-49% of their bodies.

Burn size proved to be the strongest predictor of survival, with mortality rising significantly as burn size increased. "In patient groups with burns smaller than 60% total body surface area, there were only minor increases in mortality starting at 3% and reaching up to 7%," the investigators wrote.

A large increase in mortality was noted when burn size reached 62% of the total body surface area. Such patients had a tenfold higher risk of death, compared with those who had smaller burns, the investigators reported (Lancet 2012 [doi:10.1016/S0140-6736(11)61345-7]).

Large burns also were associated with significant increases in multiorgan failure, infection during ICU stay, and the need for more surgeries to excise tissue. The rate of multiorgan failure was 6%-12% and the rate of sepsis was only 2%-6% for burns involving up to 59% of the body surface area. These rates ballooned as high as 27%-45% for multiorgan failure and 15%-26% for sepsis when burns involved 60% or more of the body surface area.

In addition, blood glucose and insulin levels rose significantly with burns involving 60% or more of the total body surface area, as did resting energy expenditure. Together with concomitant changes in liver structure and function, these findings reflect a massive hypermetabolic response to burn injury, Dr. Kraft and his associates reported.

Cytokine levels also differed by size of burn. With burns involving 60% or more of the body surface area, the levels of interleukin-6, -8, -10, and -13; macrophage inflammatory protein 1beta; tumor necrosis factor–alpha; granulocyte colony-stimulating factor; interferon-gamma; granulocyte-macrophage colony stimulating factor; and C-reactive protein rose substantially for an extended period of time.

Given these findings, "we recommend that pediatric patients with greater than 60% total body surface area burns be immediately transferred to a specialized burn center. Furthermore, at the burn center, patients should be treated with increased vigilance and improved therapies, in view of the increased risk of poor outcome associated with this burn size," the researchers wrote.

After burn size, the presence of inhalation injury in addition to external burn injury was a significant predictor of mortality. Patients who sustained inhalation injury had a threefold higher risk of death than did patients with no inhalation injuries. "We recommend that the treating physician [keep] in mind that the presence of inhalation injury significantly affects postburn outcomes," they noted.

Patient age and sex showed no association with survival, and neither did the time interval between sustaining the burn and presenting for admission.

It was noteworthy that mortality rates in this study were relatively low, even among patients who had the most extensive burns. "In our opinion, [high survival was] attributable to an improved and aggressive treatment regimen," they added.

This study was supported by Shriners Hospitals for Children, the National Institutes of Health, the National Institute on Disability and Rehabilitation Research, the Institute for Translational Sciences, the CFI Leaders Opportunity fund, and Physicians’ Services Incorporated Foundation. The investigators reported having no financial conflicts of interest.

For pediatric burn patients, the percentage of total body surface area affected remains the strongest predictor of survival, according to a report published online Jan. 31 in the Lancet.

"We have established that, in a modern pediatric burn care setting, a burn size of roughly 60% total body surface area is a crucial threshold for postburn morbidity and mortality," wrote Dr. Robert Kraft of Shriners Hospitals for Children, Galveston, Texas, and his associates.

For decades, burn size has been the main prognostic factor for both adults and children with burn injuries. But recent improvements in burn care – including novel drug treatments, new grafting techniques and materials, and improved life-support systems and monitoring methods – have dramatically improved survival, according to the investigators. Because treatment decisions, including whether to transfer a patient to a specialized burn center, are based on the probability of survival, it was important to determine whether burn size was still predictive of major complications and mortality under current treatment conditions.

To do so, Dr. Kraft and his colleagues examined outcomes in all 952 patients admitted over a 1-year period to Galveston’s Shriners Hospital with burns involving 30% or more of their total body surface area. Most of the study patients were burned on 40%-49% of their bodies.

Burn size proved to be the strongest predictor of survival, with mortality rising significantly as burn size increased. "In patient groups with burns smaller than 60% total body surface area, there were only minor increases in mortality starting at 3% and reaching up to 7%," the investigators wrote.

A large increase in mortality was noted when burn size reached 62% of the total body surface area. Such patients had a tenfold higher risk of death, compared with those who had smaller burns, the investigators reported (Lancet 2012 [doi:10.1016/S0140-6736(11)61345-7]).

Large burns also were associated with significant increases in multiorgan failure, infection during ICU stay, and the need for more surgeries to excise tissue. The rate of multiorgan failure was 6%-12% and the rate of sepsis was only 2%-6% for burns involving up to 59% of the body surface area. These rates ballooned as high as 27%-45% for multiorgan failure and 15%-26% for sepsis when burns involved 60% or more of the body surface area.

In addition, blood glucose and insulin levels rose significantly with burns involving 60% or more of the total body surface area, as did resting energy expenditure. Together with concomitant changes in liver structure and function, these findings reflect a massive hypermetabolic response to burn injury, Dr. Kraft and his associates reported.

Cytokine levels also differed by size of burn. With burns involving 60% or more of the body surface area, the levels of interleukin-6, -8, -10, and -13; macrophage inflammatory protein 1beta; tumor necrosis factor–alpha; granulocyte colony-stimulating factor; interferon-gamma; granulocyte-macrophage colony stimulating factor; and C-reactive protein rose substantially for an extended period of time.

Given these findings, "we recommend that pediatric patients with greater than 60% total body surface area burns be immediately transferred to a specialized burn center. Furthermore, at the burn center, patients should be treated with increased vigilance and improved therapies, in view of the increased risk of poor outcome associated with this burn size," the researchers wrote.

After burn size, the presence of inhalation injury in addition to external burn injury was a significant predictor of mortality. Patients who sustained inhalation injury had a threefold higher risk of death than did patients with no inhalation injuries. "We recommend that the treating physician [keep] in mind that the presence of inhalation injury significantly affects postburn outcomes," they noted.

Patient age and sex showed no association with survival, and neither did the time interval between sustaining the burn and presenting for admission.

It was noteworthy that mortality rates in this study were relatively low, even among patients who had the most extensive burns. "In our opinion, [high survival was] attributable to an improved and aggressive treatment regimen," they added.

This study was supported by Shriners Hospitals for Children, the National Institutes of Health, the National Institute on Disability and Rehabilitation Research, the Institute for Translational Sciences, the CFI Leaders Opportunity fund, and Physicians’ Services Incorporated Foundation. The investigators reported having no financial conflicts of interest.