Melanoma

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

RALEIGH, N.C. – Interactive computer-assisted patient education combined with a hands-on, dermatologist-led tutorial and monthly reminders proved successful in increasing the performance of skin self-examinations in a randomized controlled trial.

The intervention also resulted in significantly increased patient confidence in the ability to detect melanoma, Savina Aneja reported at the annual meeting of the Society for Investigative Dermatology.

The fact that the intervention was triple-pronged was probably the key to its success, added Ms. Aneja, a medical student at Case Western Reserve University in Cleveland.

"We know that patients exhibit different learning styles. ... Because we used a multimodal approach we appealed to a large number of different learning styles," she said.

The study included 210 adult patients in a university dermatology clinic. Their mean age was 53 years. Those randomized to the intervention arm completed an interactive computer-based program called Skinsafe on the day of enrollment. Developed in the United Kingdom, Skinsafe is designed to increase patient awareness of melanoma risk factors and symptoms, the importance of sun-protective behaviors, and skin self-examination. Patients spent 15-40 minutes to complete the Skinsafe program in a dermatologist’s office.

The intervention group also took part in a hands-on tutorial on skin self-examination, and they signed up to receive monthly reminders to perform them. Half of the subjects opted to be reminded via e-mail, 18% via the mail, 17% by phone call, and 15% by text message.

Patients in the both groups received a brochure on melanoma detection.

The primary study end point was self-reported change in skin self-examination rates over the course of 3 months of follow-up. At baseline, 43% of subjects performed skin self-exams at home. Three months later, 61% of controls and 79% of patients in the intervention group reported regular self-exams, Ms. Aneja said.

The subgroup that opted to receive monthly text-message reminders saw the greatest improvement. "We hypothesize that this is due to a greater degree of personalization. They could select the date and time of their monthly reminders," she said.

The text messages also were more likely to reach their intended recipient than either phone calls or letters, she noted.

A key secondary end point was the number of subjects at the study’s end who felt "very or somewhat confident" in their ability to detect melanoma. This figure rose by an absolute 10% over baseline in controls, compared with an absolute 40% increase, to 76%, in the intervention group.

Ms. Aneja reported having no financial conflicts.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

Preliminary data indicate that a single 32-mg intravenous dose of ondansetron should be avoided because it may increase the risk of QT prolongation, along with the potentially fatal arrhythmia torsades de pointes, the Food and Drug Administration has announced.

GlaxoSmithKline, which manufactures ondansetron (Zofran), is removing the 32-mg single IV dose from the antinausea and vomiting drug’s label, according to an FDA statement.

The updated label will say that ondansetron, a 5-HT₃ receptor antagonist, can continue to be used to treat adults and children with chemotherapy-induced nausea and vomiting at the dose of 0.15 mg/kg administered every 4 hours for three doses. "However, no single intravenous dose of ondansetron should exceed 16 mg due to the risk of QT prolongation," the FDA said.

The new data do not affect recommendations for oral doses of ondansetron (including the single 24-mg oral dose) used for chemotherapy-induced nausea and vomiting, the FDA noted. Recommendations on lower IV doses that are used to prevent postoperative nausea and vomiting (the other approved indication for ondansetron) also are unaffected.

Preliminary results of a study conducted by GlaxoSmithKline showed that QT prolongation "occurs in a dose-dependent manner," the FDA said. At the highest dose tested (the single 32-mg IV dose), the maximum mean difference in QTcF from placebo after baseline-correction was 20 msec. At the lower single dose tested (8 mg), the maximum mean difference in QTcF from placebo after baseline correction was 6 msec.

The FDA, which required GlaxoSmithKline to conduct the study, "will evaluate the final study results when available, and will work with GSK to explore an alternative single dose regimen that is both safe and effective for the prevention of chemotherapy-induced nausea and vomiting in adults," the FDA said.

It pointed out that ECG changes, including QT interval prolongation and torsades de pointes, have been reported in patients treated with ondansetron. In September 2011, the agency announced that it was reviewing the potential for QT prolongation with ondansetron.

Patients who have congenital long QT syndrome, heart failure, or bradyarrhythmias, or who are taking other medications that prolong the QT interval "may be at particular risk for QT prolongation" with ondansetron, the FDA warned.

The statement is available at www.fda.gov/Drugs/DrugSafety/ucm310190.htm. Serious adverse events associated with ondansetron should be reported to the FDA at 800-332-1088 or www.fda.gov/medwatch.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

RALEIGH, N.C. – Wearing glasses was associated with a significantly lower rate of developing actinic keratoses on periocular skin, according to the results of a large multicenter clinical trial.

During an average 4-year prospective follow-up conducted at 6-month intervals in the Veterans Affairs Topical Tretinoin Chemoprevention Trial, the 1,131 elderly participants, most of whom were male, developed 3,291 periocular actinic keratoses.

Copyright Dmytro Panchenko/iStockphoto.com

Patients who didn’t regularly wear eyeglasses had a 40% higher rate of developing AKs on periocular skin. This is consistent with reports in the ophthalmologic literature that eyeglasses can reduce the flux of UV radiation filtered to the periocular area, according to Dr. Kachiu C. Lee, a dermatology resident at Brown University in Providence, R.I.

Her hypothesis was that eyeglasses wearers would also have a lower rate of periocular nonmelanoma skin cancer. However, this wasn’t borne out, possibly because too few of the malignancies occurred to be able to demonstrate a protective effect, she noted. Although all suspected skin cancers were biopsied for histologic diagnosis, only 19 periocular squamous cell carcinomas and 71 periocular basal cell carcinomas occurred during follow-up.

A significant study limitation was that patients weren’t surveyed as to their use of sunglasses. "That’s a huge potential confounding variable," Dr. Lee said.

The study was sponsored by the U.S. Department of Veterans Affairs. Dr. Lee reported having no financial conflicts.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

In this month's program, Dr. Axel Hauschild discusses the results of a study that showed a 70% improvement in progression-free survival in patients with melanoma randomized to dabrafenib in the open-label break-3 trial.

Then, our reporter Heidi Splete reviews a study showing that an at-home hair removal device may work no better than standard shaving.

The Environment Protection Agency has reported that the ozone layer is improving, thanks to the worldwide ban of chlorofluorocarbons in 1989. We interviewed Drusilla Hufford at the EPA to find out more.

Cosmetic Counter host, Dr. Lily Talakoub, offers tips for educating patients about retinoids and anti-wrinkle creams. And lastly, Dr. Alan Rockoff tells a story that may induce contractions.

Don’t miss another episode of The Skinny Podcast; subscribe for free on iTunes! 

In this month's program, Dr. Axel Hauschild discusses the results of a study that showed a 70% improvement in progression-free survival in patients with melanoma randomized to dabrafenib in the open-label break-3 trial.

Then, our reporter Heidi Splete reviews a study showing that an at-home hair removal device may work no better than standard shaving.

The Environment Protection Agency has reported that the ozone layer is improving, thanks to the worldwide ban of chlorofluorocarbons in 1989. We interviewed Drusilla Hufford at the EPA to find out more.

Cosmetic Counter host, Dr. Lily Talakoub, offers tips for educating patients about retinoids and anti-wrinkle creams. And lastly, Dr. Alan Rockoff tells a story that may induce contractions.

Don’t miss another episode of The Skinny Podcast; subscribe for free on iTunes! 

In this month's program, Dr. Axel Hauschild discusses the results of a study that showed a 70% improvement in progression-free survival in patients with melanoma randomized to dabrafenib in the open-label break-3 trial.

Then, our reporter Heidi Splete reviews a study showing that an at-home hair removal device may work no better than standard shaving.

The Environment Protection Agency has reported that the ozone layer is improving, thanks to the worldwide ban of chlorofluorocarbons in 1989. We interviewed Drusilla Hufford at the EPA to find out more.

Cosmetic Counter host, Dr. Lily Talakoub, offers tips for educating patients about retinoids and anti-wrinkle creams. And lastly, Dr. Alan Rockoff tells a story that may induce contractions.

Don’t miss another episode of The Skinny Podcast; subscribe for free on iTunes! 

CHICAGO – Vemurafenib has a persistent survival benefit when given as first-line therapy for advanced BRAF-mutant melanoma, but the magnitude of benefit diminishes over time, according to an update of the BRIM-3 randomized trial.

With a median follow-up of about a year, vemurafenib was associated with a 30% relative reduction in the risk of death, relative to dacarbazine, presenting author Dr. Paul Chapman reported at the annual meeting of the American Society of Clinical Oncology. This is roughly half of the 63% relative risk reduction seen at a median follow-up of about 3 months, as reported at last year’s meeting.

The safety profile of vemurafenib was largely consistent with the earlier experience; the main high-grade adverse effects were skin toxicity (seen in about a third of patients) and liver toxicity (seen in about a tenth). But a few patients have developed second primary melanomas.

The observed temporal trend for overall survival benefit suggests "perhaps that most of the benefit in overall survival may be due to decreasing early deaths," said Dr. Chapman, an oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Discussant Dr. Michael B. Atkins of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington maintained that "the mature overall survival data [confirm] that vemurafenib is better than dacarbazine," and noted that it was "reassuring" that findings were similar, whether patients who crossed over to the vemurafenib arm were censored or not, "probably the most stringent test of survival."

However, he called attention to the fact that the median survival of 13-plus months with vemurafenib seen in BRIM-3 falls short of the 16-plus months seen in BRIM-2, a phase II trial in patients with previously treated advanced melanoma. "Did first-line patients have more aggressive disease and therefore fall off early?" he wondered. "Alternatively, was there less continuation of vemurafenib after progressive disease in the BRIM-3 trial relative to the BRIM-2 trial? If that was the case, some sort of confirmatory analysis should be done to see whether that can impact overall survival."

The decrease in vemurafenib efficacy seen over time might have several explanations, Dr. Atkins proposed. "Is it that the early, more robust hazard ratio was a manifestation of the so-called Lazarus effect, that these targeted therapies can cause patients who are really in bad shape and would have a short survival to have their survival prolonged, even though it was less than the survival of patients with less-aggressive tumors?" he wondered, echoing Dr. Chapman’s suggestion. Alternatively, maturation of the survival data might have contributed to the change in efficacy in patients with stage IIIC, M1a, and M1b disease who did not appear to benefit from vemurafenib.

In the larger context, the findings raise an important question pertaining to the clinical trials process generally, according to Dr. Atkins: "What does this say about the early analysis of trials like this, and reporting forever more that the hazard ratio is 0.35 or so, rather than what the more accurate 0.70 is?"

A Genentech spokesperson said that "due to differences in the study populations and trial designs, the results from these trials cannot be directly compared. BRIM3 was a global, randomized, Phase III trial comparing Zelboraf (vemurafenib) to DTIC chemotherapy in people with newly diagnosed BRAF V600 mutation-positive metastatic melanoma, while BRIM2 was a Phase II study that evaluated patients with previously treated disease."

The 675 patients in BRIM-3 had stage IIIC or IV melanoma harboring the BRAF V600E mutation. They were assigned evenly to intravenous dacarbazine or oral vemurafenib, the only targeted agent approved specifically for treating BRAF-mutant melanoma.

Large proportions of patients in both the vemurafenib and dacarbazine arms (36% and 44%, respectively) received other anticancer therapies after coming off the trial, Dr. Chapman reported. About a fifth of all patients in each arm went on to receive ipilimumab, and a fourth in the dacarbazine arm crossed over to vemurafenib.

Updated results – after a median follow-up of 9.5 months in the dacarbazine arm and 12.5 months in the vemurafenib arm – showed persistence of a progression-free survival benefit in favor of vemurafenib with censoring of patients at crossover (6.9 vs. 1.6 months; hazard ratio, 0.38; P less than .001).

There was also still an improvement in overall survival, regardless of whether patients were censored at crossover (13.6 vs. 9.7 months; HR, 0.70; P less than .001) or not (13.6 vs. 10.3 months; HR, 0.76; P less than .01).

The leading grade 3 or worse adverse events with vemurafenib remained cutaneous squamous cell carcinomas (seen in 19% of patients), keratoacanthomas (10%), and elevations of liver function tests (10%). In addition, eight patients developed new primary melanomas.

Dr. Chapman disclosed that he receives honoraria and research funding from Roche/Genentech. The trial was sponsored by Hoffman-LaRoche. Dr. Atkins disclosed that he is a consultant to Bristol-Myers Squibb, Celgene, Curetech, Genentech, Merck, Novartis, and Prometheus.

This article was updated on July 3, 2012.

CHICAGO – Vemurafenib has a persistent survival benefit when given as first-line therapy for advanced BRAF-mutant melanoma, but the magnitude of benefit diminishes over time, according to an update of the BRIM-3 randomized trial.

With a median follow-up of about a year, vemurafenib was associated with a 30% relative reduction in the risk of death, relative to dacarbazine, presenting author Dr. Paul Chapman reported at the annual meeting of the American Society of Clinical Oncology. This is roughly half of the 63% relative risk reduction seen at a median follow-up of about 3 months, as reported at last year’s meeting.

The safety profile of vemurafenib was largely consistent with the earlier experience; the main high-grade adverse effects were skin toxicity (seen in about a third of patients) and liver toxicity (seen in about a tenth). But a few patients have developed second primary melanomas.

The observed temporal trend for overall survival benefit suggests "perhaps that most of the benefit in overall survival may be due to decreasing early deaths," said Dr. Chapman, an oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Discussant Dr. Michael B. Atkins of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington maintained that "the mature overall survival data [confirm] that vemurafenib is better than dacarbazine," and noted that it was "reassuring" that findings were similar, whether patients who crossed over to the vemurafenib arm were censored or not, "probably the most stringent test of survival."

However, he called attention to the fact that the median survival of 13-plus months with vemurafenib seen in BRIM-3 falls short of the 16-plus months seen in BRIM-2, a phase II trial in patients with previously treated advanced melanoma. "Did first-line patients have more aggressive disease and therefore fall off early?" he wondered. "Alternatively, was there less continuation of vemurafenib after progressive disease in the BRIM-3 trial relative to the BRIM-2 trial? If that was the case, some sort of confirmatory analysis should be done to see whether that can impact overall survival."

The decrease in vemurafenib efficacy seen over time might have several explanations, Dr. Atkins proposed. "Is it that the early, more robust hazard ratio was a manifestation of the so-called Lazarus effect, that these targeted therapies can cause patients who are really in bad shape and would have a short survival to have their survival prolonged, even though it was less than the survival of patients with less-aggressive tumors?" he wondered, echoing Dr. Chapman’s suggestion. Alternatively, maturation of the survival data might have contributed to the change in efficacy in patients with stage IIIC, M1a, and M1b disease who did not appear to benefit from vemurafenib.

In the larger context, the findings raise an important question pertaining to the clinical trials process generally, according to Dr. Atkins: "What does this say about the early analysis of trials like this, and reporting forever more that the hazard ratio is 0.35 or so, rather than what the more accurate 0.70 is?"

A Genentech spokesperson said that "due to differences in the study populations and trial designs, the results from these trials cannot be directly compared. BRIM3 was a global, randomized, Phase III trial comparing Zelboraf (vemurafenib) to DTIC chemotherapy in people with newly diagnosed BRAF V600 mutation-positive metastatic melanoma, while BRIM2 was a Phase II study that evaluated patients with previously treated disease."

The 675 patients in BRIM-3 had stage IIIC or IV melanoma harboring the BRAF V600E mutation. They were assigned evenly to intravenous dacarbazine or oral vemurafenib, the only targeted agent approved specifically for treating BRAF-mutant melanoma.

Large proportions of patients in both the vemurafenib and dacarbazine arms (36% and 44%, respectively) received other anticancer therapies after coming off the trial, Dr. Chapman reported. About a fifth of all patients in each arm went on to receive ipilimumab, and a fourth in the dacarbazine arm crossed over to vemurafenib.

Updated results – after a median follow-up of 9.5 months in the dacarbazine arm and 12.5 months in the vemurafenib arm – showed persistence of a progression-free survival benefit in favor of vemurafenib with censoring of patients at crossover (6.9 vs. 1.6 months; hazard ratio, 0.38; P less than .001).

There was also still an improvement in overall survival, regardless of whether patients were censored at crossover (13.6 vs. 9.7 months; HR, 0.70; P less than .001) or not (13.6 vs. 10.3 months; HR, 0.76; P less than .01).

The leading grade 3 or worse adverse events with vemurafenib remained cutaneous squamous cell carcinomas (seen in 19% of patients), keratoacanthomas (10%), and elevations of liver function tests (10%). In addition, eight patients developed new primary melanomas.

Dr. Chapman disclosed that he receives honoraria and research funding from Roche/Genentech. The trial was sponsored by Hoffman-LaRoche. Dr. Atkins disclosed that he is a consultant to Bristol-Myers Squibb, Celgene, Curetech, Genentech, Merck, Novartis, and Prometheus.

This article was updated on July 3, 2012.

CHICAGO – Vemurafenib has a persistent survival benefit when given as first-line therapy for advanced BRAF-mutant melanoma, but the magnitude of benefit diminishes over time, according to an update of the BRIM-3 randomized trial.

With a median follow-up of about a year, vemurafenib was associated with a 30% relative reduction in the risk of death, relative to dacarbazine, presenting author Dr. Paul Chapman reported at the annual meeting of the American Society of Clinical Oncology. This is roughly half of the 63% relative risk reduction seen at a median follow-up of about 3 months, as reported at last year’s meeting.

The safety profile of vemurafenib was largely consistent with the earlier experience; the main high-grade adverse effects were skin toxicity (seen in about a third of patients) and liver toxicity (seen in about a tenth). But a few patients have developed second primary melanomas.

The observed temporal trend for overall survival benefit suggests "perhaps that most of the benefit in overall survival may be due to decreasing early deaths," said Dr. Chapman, an oncologist at Memorial Sloan-Kettering Cancer Center in New York.

Discussant Dr. Michael B. Atkins of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington maintained that "the mature overall survival data [confirm] that vemurafenib is better than dacarbazine," and noted that it was "reassuring" that findings were similar, whether patients who crossed over to the vemurafenib arm were censored or not, "probably the most stringent test of survival."

However, he called attention to the fact that the median survival of 13-plus months with vemurafenib seen in BRIM-3 falls short of the 16-plus months seen in BRIM-2, a phase II trial in patients with previously treated advanced melanoma. "Did first-line patients have more aggressive disease and therefore fall off early?" he wondered. "Alternatively, was there less continuation of vemurafenib after progressive disease in the BRIM-3 trial relative to the BRIM-2 trial? If that was the case, some sort of confirmatory analysis should be done to see whether that can impact overall survival."

The decrease in vemurafenib efficacy seen over time might have several explanations, Dr. Atkins proposed. "Is it that the early, more robust hazard ratio was a manifestation of the so-called Lazarus effect, that these targeted therapies can cause patients who are really in bad shape and would have a short survival to have their survival prolonged, even though it was less than the survival of patients with less-aggressive tumors?" he wondered, echoing Dr. Chapman’s suggestion. Alternatively, maturation of the survival data might have contributed to the change in efficacy in patients with stage IIIC, M1a, and M1b disease who did not appear to benefit from vemurafenib.

In the larger context, the findings raise an important question pertaining to the clinical trials process generally, according to Dr. Atkins: "What does this say about the early analysis of trials like this, and reporting forever more that the hazard ratio is 0.35 or so, rather than what the more accurate 0.70 is?"

A Genentech spokesperson said that "due to differences in the study populations and trial designs, the results from these trials cannot be directly compared. BRIM3 was a global, randomized, Phase III trial comparing Zelboraf (vemurafenib) to DTIC chemotherapy in people with newly diagnosed BRAF V600 mutation-positive metastatic melanoma, while BRIM2 was a Phase II study that evaluated patients with previously treated disease."

The 675 patients in BRIM-3 had stage IIIC or IV melanoma harboring the BRAF V600E mutation. They were assigned evenly to intravenous dacarbazine or oral vemurafenib, the only targeted agent approved specifically for treating BRAF-mutant melanoma.

Large proportions of patients in both the vemurafenib and dacarbazine arms (36% and 44%, respectively) received other anticancer therapies after coming off the trial, Dr. Chapman reported. About a fifth of all patients in each arm went on to receive ipilimumab, and a fourth in the dacarbazine arm crossed over to vemurafenib.

Updated results – after a median follow-up of 9.5 months in the dacarbazine arm and 12.5 months in the vemurafenib arm – showed persistence of a progression-free survival benefit in favor of vemurafenib with censoring of patients at crossover (6.9 vs. 1.6 months; hazard ratio, 0.38; P less than .001).

There was also still an improvement in overall survival, regardless of whether patients were censored at crossover (13.6 vs. 9.7 months; HR, 0.70; P less than .001) or not (13.6 vs. 10.3 months; HR, 0.76; P less than .01).

The leading grade 3 or worse adverse events with vemurafenib remained cutaneous squamous cell carcinomas (seen in 19% of patients), keratoacanthomas (10%), and elevations of liver function tests (10%). In addition, eight patients developed new primary melanomas.

Dr. Chapman disclosed that he receives honoraria and research funding from Roche/Genentech. The trial was sponsored by Hoffman-LaRoche. Dr. Atkins disclosed that he is a consultant to Bristol-Myers Squibb, Celgene, Curetech, Genentech, Merck, Novartis, and Prometheus.

This article was updated on July 3, 2012.

Dear Intern:

Well, your elective is over. So is medical school, since this is your last rotation. I get nostalgic this time of year, having graduated 40 years ago, which I’m sure you’ll agree is a ridiculously long time. Because you matched at your first choice, you are now well and truly launched.

One of my recurring sentimental notions is to note a student’s last case in medical school. Will this encounter be noteworthy; or will the whole thing end, so to speak, not with a bang but a whimper?

Looking for significance in a last case is similar to quoting people’s last words. The famous ones you hear about are usually edited, interpolated from some earlier occasion, or made up altogether. If you’ve seen people breathe their last, you know that most are not able to say much of anything, nor are their families, should they happen to be there, in any frame of mind to absorb enduring wisdom.

But lo and behold – our last encounter together on this elective has indeed turned out to be unusual, perhaps even memorable. We should discuss it.

A biopsy report just came back via fax, with the heading, "Crucial Clinical Information." We saw this patient together yesterday. Truong was the Vietnamese man in his mid-20s. A mole on his back started to grow. It got itchy, he said. It bled twice.

We examined the mole in question, along with the rest of him. As you recall, he had several moles, all black like the one in question. The irritated one was regular in outline, except for a scab in the center, consistent with having been scratched.

You remember that I was not very concerned. I said that raised moles often worry patients but aren’t usually a problem. Bleeding, moreover, is mostly a sign of minor, unrecalled trauma, a scratch while sleeping or something like that. As you’ve seen this month, patients troop in daily to complain that this mole is itchy or that one has bled. I often take these lesions off to reduce anxiety as to make the diagnosis. As a prospective primary physician, you will have to make judgments about itchy moles all the time.

I asked Truong how much the irritation bothered him. He waffled. I did the biopsy.

Here is the report: malignant melanoma, level IV, thickness at least 2.1 mm.

This is what runs through my head as I read this: At this point in my career, I am as good at judging moles as I am ever going to be. I am as clinically astute as I am ever going to be. And yet, here I am, still managing to almost miss a diagnosis in which the patient’s well-being, even his life, depends on my getting it right. In how many other cases have I (and the patient) not been so lucky? How would I know?

What lessons can I draw from this experience, and which ones can I pass on to you at your very different stage of clinical life? That because certainty is unattainable, we should take off every mole just to be sure? Every mole a patient points to? If we did that, would we be better doctors? Would we be treating patients, or our own insecurity?

It has always seemed to me that in medical practice and, in general, it is best to avoid the extremes, to be neither cavalier nor paranoid. Every passerby may assault you, every neighbor (or patient) may sue you, but it’s no good going through life treating everybody as a potential mugger or litigant. You won’t have many friends if you do that, and your patients will have a lot of unnecessary scars on their skin.

There really is something to the old saying: smart is good, lucky is better. Difficult or atypical cases can make the clever and diligent doctor look like a fool, or worse.

So perhaps your last case in medical school will come to mind from time to time as your career advances. Work hard, study hard, pay attention; become as good as you possibly can. But don’t ever get too comfortable. We try our best, but nobody always gets it right.

Good luck!

To respond to this column, e-mail Dr. Rockoff at our editorial offices at sknews@elsevier.com.

Dear Intern:

Well, your elective is over. So is medical school, since this is your last rotation. I get nostalgic this time of year, having graduated 40 years ago, which I’m sure you’ll agree is a ridiculously long time. Because you matched at your first choice, you are now well and truly launched.

One of my recurring sentimental notions is to note a student’s last case in medical school. Will this encounter be noteworthy; or will the whole thing end, so to speak, not with a bang but a whimper?

Looking for significance in a last case is similar to quoting people’s last words. The famous ones you hear about are usually edited, interpolated from some earlier occasion, or made up altogether. If you’ve seen people breathe their last, you know that most are not able to say much of anything, nor are their families, should they happen to be there, in any frame of mind to absorb enduring wisdom.

But lo and behold – our last encounter together on this elective has indeed turned out to be unusual, perhaps even memorable. We should discuss it.

A biopsy report just came back via fax, with the heading, "Crucial Clinical Information." We saw this patient together yesterday. Truong was the Vietnamese man in his mid-20s. A mole on his back started to grow. It got itchy, he said. It bled twice.

We examined the mole in question, along with the rest of him. As you recall, he had several moles, all black like the one in question. The irritated one was regular in outline, except for a scab in the center, consistent with having been scratched.

You remember that I was not very concerned. I said that raised moles often worry patients but aren’t usually a problem. Bleeding, moreover, is mostly a sign of minor, unrecalled trauma, a scratch while sleeping or something like that. As you’ve seen this month, patients troop in daily to complain that this mole is itchy or that one has bled. I often take these lesions off to reduce anxiety as to make the diagnosis. As a prospective primary physician, you will have to make judgments about itchy moles all the time.

I asked Truong how much the irritation bothered him. He waffled. I did the biopsy.

Here is the report: malignant melanoma, level IV, thickness at least 2.1 mm.

This is what runs through my head as I read this: At this point in my career, I am as good at judging moles as I am ever going to be. I am as clinically astute as I am ever going to be. And yet, here I am, still managing to almost miss a diagnosis in which the patient’s well-being, even his life, depends on my getting it right. In how many other cases have I (and the patient) not been so lucky? How would I know?

What lessons can I draw from this experience, and which ones can I pass on to you at your very different stage of clinical life? That because certainty is unattainable, we should take off every mole just to be sure? Every mole a patient points to? If we did that, would we be better doctors? Would we be treating patients, or our own insecurity?

It has always seemed to me that in medical practice and, in general, it is best to avoid the extremes, to be neither cavalier nor paranoid. Every passerby may assault you, every neighbor (or patient) may sue you, but it’s no good going through life treating everybody as a potential mugger or litigant. You won’t have many friends if you do that, and your patients will have a lot of unnecessary scars on their skin.

There really is something to the old saying: smart is good, lucky is better. Difficult or atypical cases can make the clever and diligent doctor look like a fool, or worse.

So perhaps your last case in medical school will come to mind from time to time as your career advances. Work hard, study hard, pay attention; become as good as you possibly can. But don’t ever get too comfortable. We try our best, but nobody always gets it right.

Good luck!

To respond to this column, e-mail Dr. Rockoff at our editorial offices at sknews@elsevier.com.

Dear Intern:

Well, your elective is over. So is medical school, since this is your last rotation. I get nostalgic this time of year, having graduated 40 years ago, which I’m sure you’ll agree is a ridiculously long time. Because you matched at your first choice, you are now well and truly launched.

One of my recurring sentimental notions is to note a student’s last case in medical school. Will this encounter be noteworthy; or will the whole thing end, so to speak, not with a bang but a whimper?

Looking for significance in a last case is similar to quoting people’s last words. The famous ones you hear about are usually edited, interpolated from some earlier occasion, or made up altogether. If you’ve seen people breathe their last, you know that most are not able to say much of anything, nor are their families, should they happen to be there, in any frame of mind to absorb enduring wisdom.

But lo and behold – our last encounter together on this elective has indeed turned out to be unusual, perhaps even memorable. We should discuss it.

A biopsy report just came back via fax, with the heading, "Crucial Clinical Information." We saw this patient together yesterday. Truong was the Vietnamese man in his mid-20s. A mole on his back started to grow. It got itchy, he said. It bled twice.

We examined the mole in question, along with the rest of him. As you recall, he had several moles, all black like the one in question. The irritated one was regular in outline, except for a scab in the center, consistent with having been scratched.

You remember that I was not very concerned. I said that raised moles often worry patients but aren’t usually a problem. Bleeding, moreover, is mostly a sign of minor, unrecalled trauma, a scratch while sleeping or something like that. As you’ve seen this month, patients troop in daily to complain that this mole is itchy or that one has bled. I often take these lesions off to reduce anxiety as to make the diagnosis. As a prospective primary physician, you will have to make judgments about itchy moles all the time.

I asked Truong how much the irritation bothered him. He waffled. I did the biopsy.

Here is the report: malignant melanoma, level IV, thickness at least 2.1 mm.

This is what runs through my head as I read this: At this point in my career, I am as good at judging moles as I am ever going to be. I am as clinically astute as I am ever going to be. And yet, here I am, still managing to almost miss a diagnosis in which the patient’s well-being, even his life, depends on my getting it right. In how many other cases have I (and the patient) not been so lucky? How would I know?

What lessons can I draw from this experience, and which ones can I pass on to you at your very different stage of clinical life? That because certainty is unattainable, we should take off every mole just to be sure? Every mole a patient points to? If we did that, would we be better doctors? Would we be treating patients, or our own insecurity?

It has always seemed to me that in medical practice and, in general, it is best to avoid the extremes, to be neither cavalier nor paranoid. Every passerby may assault you, every neighbor (or patient) may sue you, but it’s no good going through life treating everybody as a potential mugger or litigant. You won’t have many friends if you do that, and your patients will have a lot of unnecessary scars on their skin.

There really is something to the old saying: smart is good, lucky is better. Difficult or atypical cases can make the clever and diligent doctor look like a fool, or worse.

So perhaps your last case in medical school will come to mind from time to time as your career advances. Work hard, study hard, pay attention; become as good as you possibly can. But don’t ever get too comfortable. We try our best, but nobody always gets it right.

Good luck!

To respond to this column, e-mail Dr. Rockoff at our editorial offices at sknews@elsevier.com.

Dr. Rossi discusses melanoma in the skin of color population including the incidence and presentation of melanoma as well as factors contributing to delayed diagnosis in these patients. He also gives recommendations to physicians to help educate their patients. For more information, read Dr. Rossi's article in the May 2012 issue, "Melanoma in Skin of Color." 

Dr. Rossi discusses melanoma in the skin of color population including the incidence and presentation of melanoma as well as factors contributing to delayed diagnosis in these patients. He also gives recommendations to physicians to help educate their patients. For more information, read Dr. Rossi's article in the May 2012 issue, "Melanoma in Skin of Color." 

Dr. Rossi discusses melanoma in the skin of color population including the incidence and presentation of melanoma as well as factors contributing to delayed diagnosis in these patients. He also gives recommendations to physicians to help educate their patients. For more information, read Dr. Rossi's article in the May 2012 issue, "Melanoma in Skin of Color." 

Rhode Island joins California and Vermont to become the third state to institute restrictions on the use of tanning beds by minors.

There had been an effort to completely ban the use of tanning beds by anyone under the age of 18, but a compromise was struck. In the final bill, which passed into law without the governor's signature, minors cannot use indoor tanning beds without a prescription from a physician for ultraviolet radiation therapy or a signed consent from a parent or guardian. The parental consent has to be signed in the presence of a tanning salon employee, and it essentially has the parent acknowledge that UV radiation is a carcinogen and that exposure increases the probability of developing melanoma.

The American Academy of Dermatology applauded the state's action, and noted that in Rhode Island the incidence of melanoma in women 15 years and older increased by 24% between 2004 and 2008.

"Prevention is one of the most valuable tools that we have as dermatologists. We need to continue educating patients about the risks of indoor tanning and encouraging healthy decisions to help prevent skin cancer," Dr. Daniel M. Siegel, president of the AAD, said in a statement.

"This law is similar to bans in California and Vermont that will protect children and adolescents from the health hazards of indoor tanning and sends a strong message from the state that tanning is a dangerous behavior and should be avoided," said Dr. Siegel.

Rhode Island joins California and Vermont to become the third state to institute restrictions on the use of tanning beds by minors.

There had been an effort to completely ban the use of tanning beds by anyone under the age of 18, but a compromise was struck. In the final bill, which passed into law without the governor's signature, minors cannot use indoor tanning beds without a prescription from a physician for ultraviolet radiation therapy or a signed consent from a parent or guardian. The parental consent has to be signed in the presence of a tanning salon employee, and it essentially has the parent acknowledge that UV radiation is a carcinogen and that exposure increases the probability of developing melanoma.

The American Academy of Dermatology applauded the state's action, and noted that in Rhode Island the incidence of melanoma in women 15 years and older increased by 24% between 2004 and 2008.

"Prevention is one of the most valuable tools that we have as dermatologists. We need to continue educating patients about the risks of indoor tanning and encouraging healthy decisions to help prevent skin cancer," Dr. Daniel M. Siegel, president of the AAD, said in a statement.

"This law is similar to bans in California and Vermont that will protect children and adolescents from the health hazards of indoor tanning and sends a strong message from the state that tanning is a dangerous behavior and should be avoided," said Dr. Siegel.

Rhode Island joins California and Vermont to become the third state to institute restrictions on the use of tanning beds by minors.

There had been an effort to completely ban the use of tanning beds by anyone under the age of 18, but a compromise was struck. In the final bill, which passed into law without the governor's signature, minors cannot use indoor tanning beds without a prescription from a physician for ultraviolet radiation therapy or a signed consent from a parent or guardian. The parental consent has to be signed in the presence of a tanning salon employee, and it essentially has the parent acknowledge that UV radiation is a carcinogen and that exposure increases the probability of developing melanoma.

The American Academy of Dermatology applauded the state's action, and noted that in Rhode Island the incidence of melanoma in women 15 years and older increased by 24% between 2004 and 2008.

"Prevention is one of the most valuable tools that we have as dermatologists. We need to continue educating patients about the risks of indoor tanning and encouraging healthy decisions to help prevent skin cancer," Dr. Daniel M. Siegel, president of the AAD, said in a statement.

"This law is similar to bans in California and Vermont that will protect children and adolescents from the health hazards of indoor tanning and sends a strong message from the state that tanning is a dangerous behavior and should be avoided," said Dr. Siegel.