Melanoma

The Dermatology Foundation has conferred its Lifetime Career Educator Award on Dr. Irwin M. Braverman, professor of dermatology at Yale University School of Medicine. According to the foundation, "The award celebrates Dr. Braverman's distinguished career and the high standard he has set for the next generation of teachers in all areas of dermatology." For more information, visit www.dermatologyfoundation.org

The Dermatology Foundation has conferred its Lifetime Career Educator Award on Dr. Irwin M. Braverman, professor of dermatology at Yale University School of Medicine. According to the foundation, "The award celebrates Dr. Braverman's distinguished career and the high standard he has set for the next generation of teachers in all areas of dermatology." For more information, visit www.dermatologyfoundation.org

The Dermatology Foundation has conferred its Lifetime Career Educator Award on Dr. Irwin M. Braverman, professor of dermatology at Yale University School of Medicine. According to the foundation, "The award celebrates Dr. Braverman's distinguished career and the high standard he has set for the next generation of teachers in all areas of dermatology." For more information, visit www.dermatologyfoundation.org

SAN FRANCISCO — While the relationship of the human papillomavirus to cervical cancer is well known among the public and in the medical profession, it is less commonly recognized that oral HPV appears to be associated with head and neck cancers. Even among the cognoscenti, there is a good deal of confusion about the details of this association.

At the Seventh International Conference on Head and Neck Cancer, Dr. Maura L. Gillison of Johns Hopkins University, Baltimore, reviewed current studies to answer some of the most frequently asked questions about HPV and cancers of the head and neck:

▸ Which HPV types are most associated with cancers of the head and neck? HPV-16 is the most common cause of cervical cancer, accounting for about 54% of these cancers, followed by HPV-18 and HPV-45. HPV-16 may be even more prominent among cancers of the head and neck, with a 92% association in one study.

▸ What risk of cancer is associated with oral HPV infection? Published studies show little agreement on the magnitude of the risk associated with oral HPV-16, although all the studies that Dr. Gillison reviewed found statistically significant increases. The odds ratios in published studies range from 1.7 for all the head and neck cancers to 32.3 for cancers of the oropharynx to 99.3 for cancers of the tonsil. Dr. Gillison estimated the overall increase in the risk of oropharyngeal cancer from HPV-16 infection to be about 15-fold over the risk in people who are not infected.

▸ How common is oral HPV infection? Estimates of the prevalence of HPV infection in control populations range from 3% to 18%.

▸ What are the risk factors for oral HPV infection? As in urogenital infection, sexual behavior appears to be the prime culprit in oral HPV infection, although peripartum transmission has been documented. Several studies have found HPV-16-positive head and neck cancers to be associated with a history of sexually transmitted disease, a history of casual sex, infrequent condom use, infrequent barrier use during oral sex, the number of sexual partners, and the number of oral sex partners.

▸ How does oral infection relate to cervical infection? Oral HPV infection is about three times as likely in women with cervical infections, but in the overwhelming majority of these women—94% according to one study—different types of HPV are responsible for their oral and urogenital infections.

▸ How long is a patient with HPV-positive cancer infectious? Studies have found oral HPV infections to persist for about 2 years following treatment for head and neck cancers. These infections have not been associated with recurrences or second primary cancers, however.

▸ Will the HPV vaccine have any effect on oral HPV infection? There is no direct evidence bearing on this question, but the indirect evidence is encouraging. Following vaccination, HPV-16 IgG can be detected in oral fluid, and oral HPV-16 is seropositive with cervical HPV-16.

Dr. Gillison serves as a consultant to, receives research funding from, and collaborates with scientists employed by Merck & Co. The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — While the relationship of the human papillomavirus to cervical cancer is well known among the public and in the medical profession, it is less commonly recognized that oral HPV appears to be associated with head and neck cancers. Even among the cognoscenti, there is a good deal of confusion about the details of this association.

At the Seventh International Conference on Head and Neck Cancer, Dr. Maura L. Gillison of Johns Hopkins University, Baltimore, reviewed current studies to answer some of the most frequently asked questions about HPV and cancers of the head and neck:

▸ Which HPV types are most associated with cancers of the head and neck? HPV-16 is the most common cause of cervical cancer, accounting for about 54% of these cancers, followed by HPV-18 and HPV-45. HPV-16 may be even more prominent among cancers of the head and neck, with a 92% association in one study.

▸ What risk of cancer is associated with oral HPV infection? Published studies show little agreement on the magnitude of the risk associated with oral HPV-16, although all the studies that Dr. Gillison reviewed found statistically significant increases. The odds ratios in published studies range from 1.7 for all the head and neck cancers to 32.3 for cancers of the oropharynx to 99.3 for cancers of the tonsil. Dr. Gillison estimated the overall increase in the risk of oropharyngeal cancer from HPV-16 infection to be about 15-fold over the risk in people who are not infected.

▸ How common is oral HPV infection? Estimates of the prevalence of HPV infection in control populations range from 3% to 18%.

▸ What are the risk factors for oral HPV infection? As in urogenital infection, sexual behavior appears to be the prime culprit in oral HPV infection, although peripartum transmission has been documented. Several studies have found HPV-16-positive head and neck cancers to be associated with a history of sexually transmitted disease, a history of casual sex, infrequent condom use, infrequent barrier use during oral sex, the number of sexual partners, and the number of oral sex partners.

▸ How does oral infection relate to cervical infection? Oral HPV infection is about three times as likely in women with cervical infections, but in the overwhelming majority of these women—94% according to one study—different types of HPV are responsible for their oral and urogenital infections.

▸ How long is a patient with HPV-positive cancer infectious? Studies have found oral HPV infections to persist for about 2 years following treatment for head and neck cancers. These infections have not been associated with recurrences or second primary cancers, however.

▸ Will the HPV vaccine have any effect on oral HPV infection? There is no direct evidence bearing on this question, but the indirect evidence is encouraging. Following vaccination, HPV-16 IgG can be detected in oral fluid, and oral HPV-16 is seropositive with cervical HPV-16.

Dr. Gillison serves as a consultant to, receives research funding from, and collaborates with scientists employed by Merck & Co. The conference was sponsored by the American Head and Neck Society.

SAN FRANCISCO — While the relationship of the human papillomavirus to cervical cancer is well known among the public and in the medical profession, it is less commonly recognized that oral HPV appears to be associated with head and neck cancers. Even among the cognoscenti, there is a good deal of confusion about the details of this association.

At the Seventh International Conference on Head and Neck Cancer, Dr. Maura L. Gillison of Johns Hopkins University, Baltimore, reviewed current studies to answer some of the most frequently asked questions about HPV and cancers of the head and neck:

▸ Which HPV types are most associated with cancers of the head and neck? HPV-16 is the most common cause of cervical cancer, accounting for about 54% of these cancers, followed by HPV-18 and HPV-45. HPV-16 may be even more prominent among cancers of the head and neck, with a 92% association in one study.

▸ What risk of cancer is associated with oral HPV infection? Published studies show little agreement on the magnitude of the risk associated with oral HPV-16, although all the studies that Dr. Gillison reviewed found statistically significant increases. The odds ratios in published studies range from 1.7 for all the head and neck cancers to 32.3 for cancers of the oropharynx to 99.3 for cancers of the tonsil. Dr. Gillison estimated the overall increase in the risk of oropharyngeal cancer from HPV-16 infection to be about 15-fold over the risk in people who are not infected.

▸ How common is oral HPV infection? Estimates of the prevalence of HPV infection in control populations range from 3% to 18%.

▸ What are the risk factors for oral HPV infection? As in urogenital infection, sexual behavior appears to be the prime culprit in oral HPV infection, although peripartum transmission has been documented. Several studies have found HPV-16-positive head and neck cancers to be associated with a history of sexually transmitted disease, a history of casual sex, infrequent condom use, infrequent barrier use during oral sex, the number of sexual partners, and the number of oral sex partners.

▸ How does oral infection relate to cervical infection? Oral HPV infection is about three times as likely in women with cervical infections, but in the overwhelming majority of these women—94% according to one study—different types of HPV are responsible for their oral and urogenital infections.

▸ How long is a patient with HPV-positive cancer infectious? Studies have found oral HPV infections to persist for about 2 years following treatment for head and neck cancers. These infections have not been associated with recurrences or second primary cancers, however.

▸ Will the HPV vaccine have any effect on oral HPV infection? There is no direct evidence bearing on this question, but the indirect evidence is encouraging. Following vaccination, HPV-16 IgG can be detected in oral fluid, and oral HPV-16 is seropositive with cervical HPV-16.

Dr. Gillison serves as a consultant to, receives research funding from, and collaborates with scientists employed by Merck & Co. The conference was sponsored by the American Head and Neck Society.

MONTREAL — Formation of an international confocal microscopy group, software that aids the detection and mapping of skin lesions, and introduction of a handheld device are among recent advances to aid in the diagnosis of lentigo maligna and other lesions in real time.

Researchers hope widespread adoption of confocal laser microscopy progress will permit further early diagnoses of cutaneous melanoma and other lesions at the bedside. "It is critical to do biopsies early. If you believe cancer starts from a single cell, you can diagnose it early [with confocal laser microscopy]. That is what we are working on now," Dr. Richard Langley said.

Described as a "living skin biopsy" by some, microscopy is not new. Pathologists have employed the intensely focused light to examine tissue specimens since the 1950s, he said. There is a limitation in live patients, however. "We cannot go through a patient's skin, so we deal with reflective light. We still have confocal concepts, but we have real-time results," Dr. Langley said at the annual conference of the Canadian Dermatology Association.

Dr. Langley and his colleagues were the first to report use of confocal laser microscopy in a series of 40 dermatology patients with superficial melanoma (J. Am. Acad. Dermatol. 2001;45:365–76).

Others have since validated that microscopy distinguishes between malignant and benign lesions in vivo. To date, studies include more than 400 patients, said Dr. Langley of Dalhousie University, Halifax, N.S.

Last year, he and his associates published the first prospective study to compare microscopy with dermoscopy. "We decided to see if we can do a prospective, blinded, single-institution study," he said.

They assessed 125 patients with suspicious pigmented lesions using both technologies, followed by a confirmatory biopsy (Dermatology 2007;215:365–72). They detected a total of 88 melanotic nevi and 37 melanomas. "Sensitivity was higher with confocal versus dermoscopy [97% vs. 89%, respectively]. The specificity was about the same [83% vs. 84%]," Dr. Langley said. "We missed one melanoma with the confocal technology, so it was not perfect."

For dermatologists accustomed to reading cross-sectional biopsies, it may take an adjustment to recognize the clusters of melanocytes, Dr. Langley said. "You have to retrain your eye to look differently—you are looking from above. Also, it is in black and white, not color, like we're used to."

Indicative of the growing interest in this technology is the formation of the International Confocal Microscopy Working Group, launched at the February 2008 American Academy of Dermatology annual meeting in San Antonio. The group aims to form an international network of medical professionals working with confocal laser microscopy and to promote education, training, and additional research about the technology.

New software for microscopy also emerged in the past year (Electronic Zoom, Lucid Inc.). The video-capture software allows dermatologists or dermatopathologists to map a lesion and tag an area of interest. "You start with a macro image and, if you see an area you want to focus on, the software can be engaged," Dr. Langley said.

Another advance is the availability of a hand-held confocal microscopy device (VivaScope 3000, Lucid). Dr. Langley had no relevant financial disclosures.

A hand-held confocal microscopy device is one recent dermoscopy advancement. ©Lucid, Inc.

MONTREAL — Formation of an international confocal microscopy group, software that aids the detection and mapping of skin lesions, and introduction of a handheld device are among recent advances to aid in the diagnosis of lentigo maligna and other lesions in real time.

Researchers hope widespread adoption of confocal laser microscopy progress will permit further early diagnoses of cutaneous melanoma and other lesions at the bedside. "It is critical to do biopsies early. If you believe cancer starts from a single cell, you can diagnose it early [with confocal laser microscopy]. That is what we are working on now," Dr. Richard Langley said.

Described as a "living skin biopsy" by some, microscopy is not new. Pathologists have employed the intensely focused light to examine tissue specimens since the 1950s, he said. There is a limitation in live patients, however. "We cannot go through a patient's skin, so we deal with reflective light. We still have confocal concepts, but we have real-time results," Dr. Langley said at the annual conference of the Canadian Dermatology Association.

Dr. Langley and his colleagues were the first to report use of confocal laser microscopy in a series of 40 dermatology patients with superficial melanoma (J. Am. Acad. Dermatol. 2001;45:365–76).

Others have since validated that microscopy distinguishes between malignant and benign lesions in vivo. To date, studies include more than 400 patients, said Dr. Langley of Dalhousie University, Halifax, N.S.

Last year, he and his associates published the first prospective study to compare microscopy with dermoscopy. "We decided to see if we can do a prospective, blinded, single-institution study," he said.

They assessed 125 patients with suspicious pigmented lesions using both technologies, followed by a confirmatory biopsy (Dermatology 2007;215:365–72). They detected a total of 88 melanotic nevi and 37 melanomas. "Sensitivity was higher with confocal versus dermoscopy [97% vs. 89%, respectively]. The specificity was about the same [83% vs. 84%]," Dr. Langley said. "We missed one melanoma with the confocal technology, so it was not perfect."

For dermatologists accustomed to reading cross-sectional biopsies, it may take an adjustment to recognize the clusters of melanocytes, Dr. Langley said. "You have to retrain your eye to look differently—you are looking from above. Also, it is in black and white, not color, like we're used to."

Indicative of the growing interest in this technology is the formation of the International Confocal Microscopy Working Group, launched at the February 2008 American Academy of Dermatology annual meeting in San Antonio. The group aims to form an international network of medical professionals working with confocal laser microscopy and to promote education, training, and additional research about the technology.

New software for microscopy also emerged in the past year (Electronic Zoom, Lucid Inc.). The video-capture software allows dermatologists or dermatopathologists to map a lesion and tag an area of interest. "You start with a macro image and, if you see an area you want to focus on, the software can be engaged," Dr. Langley said.

Another advance is the availability of a hand-held confocal microscopy device (VivaScope 3000, Lucid). Dr. Langley had no relevant financial disclosures.

A hand-held confocal microscopy device is one recent dermoscopy advancement. ©Lucid, Inc.

MONTREAL — Formation of an international confocal microscopy group, software that aids the detection and mapping of skin lesions, and introduction of a handheld device are among recent advances to aid in the diagnosis of lentigo maligna and other lesions in real time.

Researchers hope widespread adoption of confocal laser microscopy progress will permit further early diagnoses of cutaneous melanoma and other lesions at the bedside. "It is critical to do biopsies early. If you believe cancer starts from a single cell, you can diagnose it early [with confocal laser microscopy]. That is what we are working on now," Dr. Richard Langley said.

Described as a "living skin biopsy" by some, microscopy is not new. Pathologists have employed the intensely focused light to examine tissue specimens since the 1950s, he said. There is a limitation in live patients, however. "We cannot go through a patient's skin, so we deal with reflective light. We still have confocal concepts, but we have real-time results," Dr. Langley said at the annual conference of the Canadian Dermatology Association.

Dr. Langley and his colleagues were the first to report use of confocal laser microscopy in a series of 40 dermatology patients with superficial melanoma (J. Am. Acad. Dermatol. 2001;45:365–76).

Others have since validated that microscopy distinguishes between malignant and benign lesions in vivo. To date, studies include more than 400 patients, said Dr. Langley of Dalhousie University, Halifax, N.S.

Last year, he and his associates published the first prospective study to compare microscopy with dermoscopy. "We decided to see if we can do a prospective, blinded, single-institution study," he said.

They assessed 125 patients with suspicious pigmented lesions using both technologies, followed by a confirmatory biopsy (Dermatology 2007;215:365–72). They detected a total of 88 melanotic nevi and 37 melanomas. "Sensitivity was higher with confocal versus dermoscopy [97% vs. 89%, respectively]. The specificity was about the same [83% vs. 84%]," Dr. Langley said. "We missed one melanoma with the confocal technology, so it was not perfect."

For dermatologists accustomed to reading cross-sectional biopsies, it may take an adjustment to recognize the clusters of melanocytes, Dr. Langley said. "You have to retrain your eye to look differently—you are looking from above. Also, it is in black and white, not color, like we're used to."

Indicative of the growing interest in this technology is the formation of the International Confocal Microscopy Working Group, launched at the February 2008 American Academy of Dermatology annual meeting in San Antonio. The group aims to form an international network of medical professionals working with confocal laser microscopy and to promote education, training, and additional research about the technology.

New software for microscopy also emerged in the past year (Electronic Zoom, Lucid Inc.). The video-capture software allows dermatologists or dermatopathologists to map a lesion and tag an area of interest. "You start with a macro image and, if you see an area you want to focus on, the software can be engaged," Dr. Langley said.

Another advance is the availability of a hand-held confocal microscopy device (VivaScope 3000, Lucid). Dr. Langley had no relevant financial disclosures.

A hand-held confocal microscopy device is one recent dermoscopy advancement. ©Lucid, Inc.

MONTREAL — Regression of a thin melanoma should not be the sole criterion to justify a sentinel lymph node biopsy, according to a retrospective study.

Regression alone is insufficient in the absence of other recognized high-risk predictors of sentinel lymph node (SLN) involvement, Dr. Pierre-Luc Dion said. More established risk factors include Breslow thickness greater than 1 mm, Clark level IV or V, and lesion ulceration.

Prognosis generally is better with thinner melanoma. Identification of the minority of thin melanoma patients who are at high risk for metastasis, however, remains a clinical challenge.

"There is an ongoing debate if regression is good news or bad news for patients. Some think it shows an immune response against tumor cells, but others say it can lead to an underestimation of the real thickness," Dr. Dion said at the annual conference of the Canadian Dermatology Association.

There is no consensus in the literature. One study of 65 thin melanomas with regression found that only 2 lesions (3%) had a positive SLN biopsy result (Ann. Surg. Oncol. 2003;10:558–61).

Another study found only 1 patient with a positive SLN biopsy among 344 who had thin melanomas (mean Breslow thickness of 1.1 mm) that had shown histologic regression (Ann. Surg. Oncol. 2008;15:316–22).

Other investigators have proposed that tumor regression predicts a higher risk of sentinel node involvement in thin melanomas (Br. J. Dermatol. 2003;149:662–3).

Dr. Dion and his colleagues assessed 693 patients treated at the melanoma clinics for Le Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec in Saint-Nicolas and Québec City. All of the patients underwent sentinel lymph node biopsy between 1996 and 2007. The median Breslow thickness was 2.28 mm and mean age was 55 years.

A total of 653 patients had a lesion that was greater than 1 mm. Their prognoses were compared with those of a group of 40 others with thinner melanoma and regression. Regression was determined by a pathologist, who found at least a 15% reduction in the lesion size on multiple slides.

Among the patients with regression, none had a positive lymph node, compared with 146 (22%) in the control group, suggesting regression alone is not a reliable predictor, said Dr. Dion of the hospital in Saint-Nicolas.

Of the 40 patients, 1 experienced complete regression. Another six patients in this group developed in situ melanoma. The median Breslow thickness among the remaining 33 patients was 0.6 mm. At a mean follow-up of almost 4 years, recurrence occurred in two patients, including one local recurrence and one transit metastasis, Dr. Dion said.

MONTREAL — Regression of a thin melanoma should not be the sole criterion to justify a sentinel lymph node biopsy, according to a retrospective study.

Regression alone is insufficient in the absence of other recognized high-risk predictors of sentinel lymph node (SLN) involvement, Dr. Pierre-Luc Dion said. More established risk factors include Breslow thickness greater than 1 mm, Clark level IV or V, and lesion ulceration.

Prognosis generally is better with thinner melanoma. Identification of the minority of thin melanoma patients who are at high risk for metastasis, however, remains a clinical challenge.

"There is an ongoing debate if regression is good news or bad news for patients. Some think it shows an immune response against tumor cells, but others say it can lead to an underestimation of the real thickness," Dr. Dion said at the annual conference of the Canadian Dermatology Association.

There is no consensus in the literature. One study of 65 thin melanomas with regression found that only 2 lesions (3%) had a positive SLN biopsy result (Ann. Surg. Oncol. 2003;10:558–61).

Another study found only 1 patient with a positive SLN biopsy among 344 who had thin melanomas (mean Breslow thickness of 1.1 mm) that had shown histologic regression (Ann. Surg. Oncol. 2008;15:316–22).

Other investigators have proposed that tumor regression predicts a higher risk of sentinel node involvement in thin melanomas (Br. J. Dermatol. 2003;149:662–3).

Dr. Dion and his colleagues assessed 693 patients treated at the melanoma clinics for Le Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec in Saint-Nicolas and Québec City. All of the patients underwent sentinel lymph node biopsy between 1996 and 2007. The median Breslow thickness was 2.28 mm and mean age was 55 years.

A total of 653 patients had a lesion that was greater than 1 mm. Their prognoses were compared with those of a group of 40 others with thinner melanoma and regression. Regression was determined by a pathologist, who found at least a 15% reduction in the lesion size on multiple slides.

Among the patients with regression, none had a positive lymph node, compared with 146 (22%) in the control group, suggesting regression alone is not a reliable predictor, said Dr. Dion of the hospital in Saint-Nicolas.

Of the 40 patients, 1 experienced complete regression. Another six patients in this group developed in situ melanoma. The median Breslow thickness among the remaining 33 patients was 0.6 mm. At a mean follow-up of almost 4 years, recurrence occurred in two patients, including one local recurrence and one transit metastasis, Dr. Dion said.

MONTREAL — Regression of a thin melanoma should not be the sole criterion to justify a sentinel lymph node biopsy, according to a retrospective study.

Regression alone is insufficient in the absence of other recognized high-risk predictors of sentinel lymph node (SLN) involvement, Dr. Pierre-Luc Dion said. More established risk factors include Breslow thickness greater than 1 mm, Clark level IV or V, and lesion ulceration.

Prognosis generally is better with thinner melanoma. Identification of the minority of thin melanoma patients who are at high risk for metastasis, however, remains a clinical challenge.

"There is an ongoing debate if regression is good news or bad news for patients. Some think it shows an immune response against tumor cells, but others say it can lead to an underestimation of the real thickness," Dr. Dion said at the annual conference of the Canadian Dermatology Association.

There is no consensus in the literature. One study of 65 thin melanomas with regression found that only 2 lesions (3%) had a positive SLN biopsy result (Ann. Surg. Oncol. 2003;10:558–61).

Another study found only 1 patient with a positive SLN biopsy among 344 who had thin melanomas (mean Breslow thickness of 1.1 mm) that had shown histologic regression (Ann. Surg. Oncol. 2008;15:316–22).

Other investigators have proposed that tumor regression predicts a higher risk of sentinel node involvement in thin melanomas (Br. J. Dermatol. 2003;149:662–3).

Dr. Dion and his colleagues assessed 693 patients treated at the melanoma clinics for Le Centre Hospitalier Universitaire de Québec-L'Hôtel-Dieu de Québec in Saint-Nicolas and Québec City. All of the patients underwent sentinel lymph node biopsy between 1996 and 2007. The median Breslow thickness was 2.28 mm and mean age was 55 years.

A total of 653 patients had a lesion that was greater than 1 mm. Their prognoses were compared with those of a group of 40 others with thinner melanoma and regression. Regression was determined by a pathologist, who found at least a 15% reduction in the lesion size on multiple slides.

Among the patients with regression, none had a positive lymph node, compared with 146 (22%) in the control group, suggesting regression alone is not a reliable predictor, said Dr. Dion of the hospital in Saint-Nicolas.

Of the 40 patients, 1 experienced complete regression. Another six patients in this group developed in situ melanoma. The median Breslow thickness among the remaining 33 patients was 0.6 mm. At a mean follow-up of almost 4 years, recurrence occurred in two patients, including one local recurrence and one transit metastasis, Dr. Dion said.

KYOTO, JAPAN — Intratumoral interferon-gamma gene therapy delivered via an adenoviral vector induces systemic as well as local immune responses in patients with primary cutaneous T- or B-cell lymphoma, reported Dr. Mirjana Urosevic reported.

This novel approach to interferon-gamma gene transfer using an intralesionally injected adenoviral vector showed impressive safety and tolerability as well as promising efficacy in a multicenter combined phase I/II clinical trial, according to Dr. Urosevic of the University of Zürich.

Recombinant interferon-alfa and -gamma therapy have demonstrated efficacy in primary cutaneous lymphomas. However, it is accompanied by severe systemic toxicity, she said at an international investigative dermatology meeting.

Dr. Urosevic and her coworkers believe that placing substantial quantities of the interferon-gamma gene within a tumor will result in production of sustained high levels of the cytokine by the patient's own cells without systemic toxicity.

Incorporating the interferon-gamma gene into an adenoviral vector offers a substantial bonus, she said: The vector itself appears to have therapeutic efficacy. The nonreplicating recombinant adenovirus Dr. Urosevic and her colleagues are using, known as TG1042, activates interferon-alfa genes, resulting in increased intralesional expression of interferon-alfa, supplementing the tumor-rejecting effects of the transgene-induced interferon-gamma.

She reported on 33 evaluable patients who received the investigational gene therapy at six centers in Switzerland, Germany, and France in an open-label clinical trial. Twenty-eight had cutaneous T-cell lymphoma and five had cutaneous B-cell lymphoma. All had advanced disease and previously had failed to respond to at least two first-line forms of therapy.

The injected tumors showed a partial response in 10 patients and a complete response in 9 others, for an overall 57% local clinical response rate. Half of the cutaneous T-cell lymphoma patients had a local therapeutic response, as did, notably, all five with cutaneous B-cell lymphomas, she said.

Fourteen patients experienced global responses, with regression of untreated as well as treated lesions. Seven of these patients had complete responses, while the rest demonstrated partial responses.

The treatment regimen consisted of once-weekly intratumoral injection of 3×1011 viral particles for 3 weeks, then a 2-week break, followed by a patient evaluation. If the patient was stable or had at least a partial response, then treatment resumed; if the disease progressed, treatment stopped. These three-injection cycles were repeated for up to 12 cycles, or 36 injections, Dr. Urosevic reported at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

All patients have mounted neutralizing antiadenovirus antibodies in response to the vector. However, these antibodies have not blocked the interferon response to the gene transfer or the vector itself, she said.

The study was sponsored by Transgene of Strasbourg, France.

KYOTO, JAPAN — Intratumoral interferon-gamma gene therapy delivered via an adenoviral vector induces systemic as well as local immune responses in patients with primary cutaneous T- or B-cell lymphoma, reported Dr. Mirjana Urosevic reported.

This novel approach to interferon-gamma gene transfer using an intralesionally injected adenoviral vector showed impressive safety and tolerability as well as promising efficacy in a multicenter combined phase I/II clinical trial, according to Dr. Urosevic of the University of Zürich.

Recombinant interferon-alfa and -gamma therapy have demonstrated efficacy in primary cutaneous lymphomas. However, it is accompanied by severe systemic toxicity, she said at an international investigative dermatology meeting.

Dr. Urosevic and her coworkers believe that placing substantial quantities of the interferon-gamma gene within a tumor will result in production of sustained high levels of the cytokine by the patient's own cells without systemic toxicity.

Incorporating the interferon-gamma gene into an adenoviral vector offers a substantial bonus, she said: The vector itself appears to have therapeutic efficacy. The nonreplicating recombinant adenovirus Dr. Urosevic and her colleagues are using, known as TG1042, activates interferon-alfa genes, resulting in increased intralesional expression of interferon-alfa, supplementing the tumor-rejecting effects of the transgene-induced interferon-gamma.

She reported on 33 evaluable patients who received the investigational gene therapy at six centers in Switzerland, Germany, and France in an open-label clinical trial. Twenty-eight had cutaneous T-cell lymphoma and five had cutaneous B-cell lymphoma. All had advanced disease and previously had failed to respond to at least two first-line forms of therapy.

The injected tumors showed a partial response in 10 patients and a complete response in 9 others, for an overall 57% local clinical response rate. Half of the cutaneous T-cell lymphoma patients had a local therapeutic response, as did, notably, all five with cutaneous B-cell lymphomas, she said.

Fourteen patients experienced global responses, with regression of untreated as well as treated lesions. Seven of these patients had complete responses, while the rest demonstrated partial responses.

The treatment regimen consisted of once-weekly intratumoral injection of 3×1011 viral particles for 3 weeks, then a 2-week break, followed by a patient evaluation. If the patient was stable or had at least a partial response, then treatment resumed; if the disease progressed, treatment stopped. These three-injection cycles were repeated for up to 12 cycles, or 36 injections, Dr. Urosevic reported at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

All patients have mounted neutralizing antiadenovirus antibodies in response to the vector. However, these antibodies have not blocked the interferon response to the gene transfer or the vector itself, she said.

The study was sponsored by Transgene of Strasbourg, France.

KYOTO, JAPAN — Intratumoral interferon-gamma gene therapy delivered via an adenoviral vector induces systemic as well as local immune responses in patients with primary cutaneous T- or B-cell lymphoma, reported Dr. Mirjana Urosevic reported.

This novel approach to interferon-gamma gene transfer using an intralesionally injected adenoviral vector showed impressive safety and tolerability as well as promising efficacy in a multicenter combined phase I/II clinical trial, according to Dr. Urosevic of the University of Zürich.

Recombinant interferon-alfa and -gamma therapy have demonstrated efficacy in primary cutaneous lymphomas. However, it is accompanied by severe systemic toxicity, she said at an international investigative dermatology meeting.

Dr. Urosevic and her coworkers believe that placing substantial quantities of the interferon-gamma gene within a tumor will result in production of sustained high levels of the cytokine by the patient's own cells without systemic toxicity.

Incorporating the interferon-gamma gene into an adenoviral vector offers a substantial bonus, she said: The vector itself appears to have therapeutic efficacy. The nonreplicating recombinant adenovirus Dr. Urosevic and her colleagues are using, known as TG1042, activates interferon-alfa genes, resulting in increased intralesional expression of interferon-alfa, supplementing the tumor-rejecting effects of the transgene-induced interferon-gamma.

She reported on 33 evaluable patients who received the investigational gene therapy at six centers in Switzerland, Germany, and France in an open-label clinical trial. Twenty-eight had cutaneous T-cell lymphoma and five had cutaneous B-cell lymphoma. All had advanced disease and previously had failed to respond to at least two first-line forms of therapy.

The injected tumors showed a partial response in 10 patients and a complete response in 9 others, for an overall 57% local clinical response rate. Half of the cutaneous T-cell lymphoma patients had a local therapeutic response, as did, notably, all five with cutaneous B-cell lymphomas, she said.

Fourteen patients experienced global responses, with regression of untreated as well as treated lesions. Seven of these patients had complete responses, while the rest demonstrated partial responses.

The treatment regimen consisted of once-weekly intratumoral injection of 3×1011 viral particles for 3 weeks, then a 2-week break, followed by a patient evaluation. If the patient was stable or had at least a partial response, then treatment resumed; if the disease progressed, treatment stopped. These three-injection cycles were repeated for up to 12 cycles, or 36 injections, Dr. Urosevic reported at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

All patients have mounted neutralizing antiadenovirus antibodies in response to the vector. However, these antibodies have not blocked the interferon response to the gene transfer or the vector itself, she said.

The study was sponsored by Transgene of Strasbourg, France.

VANCOUVER — Compared with the lidocaine concentration typically used for local anesthesia during Mohs surgery, a lower concentration achieved equivalent pain relief with a 53% reduction in the total dose administered in a randomized, double-blind trial of 149 patients.

"We found in our clinic that 10%-15% of our patients were actually exceeding the recommended lidocaine dose of 7 mg/kg when we used 1% lidocaine with 1:100,000 epinephrine, which is the most common concentration of lidocaine used for Mohs surgery," explained Pamela Morganroth, noting that the patients nonetheless did not experience any symptoms.

"These patients often have large tumors, multiple sites, and extensive reconstructions," she said at the annual meeting of the American College of Mohs Surgery.

Minimizing lidocaine dose is important because symptoms of lidocaine toxicity occur in a dose-dependent manner; moreover, exceeding the recommended limit—even if symptoms do not occur or occur as a result of other conditions—exposes surgeons to medicolegal risk, observed Ms. Morganroth, a medical student at the University of Pennsylvania, Philadelphia.

"Unfortunately, multiple factors influence lidocaine dose," including older age; pregnancy; and renal, cardiac, and hepatic impairment, she added, "so it's virtually impossible to set a uniform maximum recommended lidocaine dose."

In the study, patients undergoing Mohs surgery were randomly assigned to local anesthesia consisting of 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine. Surgery was performed by a single physician who was unaware of the patient's assignment. The surgical field was infiltrated immediately before each Mohs layer and the reconstruction, with use of local infiltration and field blocks instead of regional nerve blocks. Excision began as soon as the patient reported no pain to a pinprick stimulus.

Outcomes included the total lidocaine dose administered (including all stages of Mohs surgery and the reconstruction) and patient comfort, which was measured subjectively with a 100-mm visual analog scale and objectively according to the volume of "rescue" lidocaine administered during the surgery. Analyses were based on 74 patients (with 83 tumors) in the 1.0% lidocaine group and 75 patients (with 85 tumors) in the 0.5% lidocaine group.

The mean total dose of lidocaine administered to patients in the 0.5% group was significantly lower, by 53%, than that administered to patients in the 1.0% group (139 mg vs. 297 mg). Mean scores for patient-rated pain (3.88 vs. 3.11 mm, respectively) or mean volume of rescue lidocaine administered (0.85 vs. 0.33 cc) did not differ significantly, Ms. Morganroth reported.

It appears that "0.5% lidocaine provides equivalent patient comfort at half the total dose of lidocaine as compared to 1.0% lidocaine," she said, while also acknowledging that the study did not measure blood levels of the drug.

"Our study demonstrates that 0.5% lidocaine decreases the risk of dose-dependent lidocaine toxicity without compromising patient comfort during Mohs surgery," said Ms. Morganroth, who reported having no conflicts of interest.

VANCOUVER — Compared with the lidocaine concentration typically used for local anesthesia during Mohs surgery, a lower concentration achieved equivalent pain relief with a 53% reduction in the total dose administered in a randomized, double-blind trial of 149 patients.

"We found in our clinic that 10%-15% of our patients were actually exceeding the recommended lidocaine dose of 7 mg/kg when we used 1% lidocaine with 1:100,000 epinephrine, which is the most common concentration of lidocaine used for Mohs surgery," explained Pamela Morganroth, noting that the patients nonetheless did not experience any symptoms.

"These patients often have large tumors, multiple sites, and extensive reconstructions," she said at the annual meeting of the American College of Mohs Surgery.

Minimizing lidocaine dose is important because symptoms of lidocaine toxicity occur in a dose-dependent manner; moreover, exceeding the recommended limit—even if symptoms do not occur or occur as a result of other conditions—exposes surgeons to medicolegal risk, observed Ms. Morganroth, a medical student at the University of Pennsylvania, Philadelphia.

"Unfortunately, multiple factors influence lidocaine dose," including older age; pregnancy; and renal, cardiac, and hepatic impairment, she added, "so it's virtually impossible to set a uniform maximum recommended lidocaine dose."

In the study, patients undergoing Mohs surgery were randomly assigned to local anesthesia consisting of 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine. Surgery was performed by a single physician who was unaware of the patient's assignment. The surgical field was infiltrated immediately before each Mohs layer and the reconstruction, with use of local infiltration and field blocks instead of regional nerve blocks. Excision began as soon as the patient reported no pain to a pinprick stimulus.

Outcomes included the total lidocaine dose administered (including all stages of Mohs surgery and the reconstruction) and patient comfort, which was measured subjectively with a 100-mm visual analog scale and objectively according to the volume of "rescue" lidocaine administered during the surgery. Analyses were based on 74 patients (with 83 tumors) in the 1.0% lidocaine group and 75 patients (with 85 tumors) in the 0.5% lidocaine group.

The mean total dose of lidocaine administered to patients in the 0.5% group was significantly lower, by 53%, than that administered to patients in the 1.0% group (139 mg vs. 297 mg). Mean scores for patient-rated pain (3.88 vs. 3.11 mm, respectively) or mean volume of rescue lidocaine administered (0.85 vs. 0.33 cc) did not differ significantly, Ms. Morganroth reported.

It appears that "0.5% lidocaine provides equivalent patient comfort at half the total dose of lidocaine as compared to 1.0% lidocaine," she said, while also acknowledging that the study did not measure blood levels of the drug.

"Our study demonstrates that 0.5% lidocaine decreases the risk of dose-dependent lidocaine toxicity without compromising patient comfort during Mohs surgery," said Ms. Morganroth, who reported having no conflicts of interest.

VANCOUVER — Compared with the lidocaine concentration typically used for local anesthesia during Mohs surgery, a lower concentration achieved equivalent pain relief with a 53% reduction in the total dose administered in a randomized, double-blind trial of 149 patients.

"We found in our clinic that 10%-15% of our patients were actually exceeding the recommended lidocaine dose of 7 mg/kg when we used 1% lidocaine with 1:100,000 epinephrine, which is the most common concentration of lidocaine used for Mohs surgery," explained Pamela Morganroth, noting that the patients nonetheless did not experience any symptoms.

"These patients often have large tumors, multiple sites, and extensive reconstructions," she said at the annual meeting of the American College of Mohs Surgery.

Minimizing lidocaine dose is important because symptoms of lidocaine toxicity occur in a dose-dependent manner; moreover, exceeding the recommended limit—even if symptoms do not occur or occur as a result of other conditions—exposes surgeons to medicolegal risk, observed Ms. Morganroth, a medical student at the University of Pennsylvania, Philadelphia.

"Unfortunately, multiple factors influence lidocaine dose," including older age; pregnancy; and renal, cardiac, and hepatic impairment, she added, "so it's virtually impossible to set a uniform maximum recommended lidocaine dose."

In the study, patients undergoing Mohs surgery were randomly assigned to local anesthesia consisting of 1.0% lidocaine with 1:100,000 epinephrine or 0.5% lidocaine with 1:200,000 epinephrine. Surgery was performed by a single physician who was unaware of the patient's assignment. The surgical field was infiltrated immediately before each Mohs layer and the reconstruction, with use of local infiltration and field blocks instead of regional nerve blocks. Excision began as soon as the patient reported no pain to a pinprick stimulus.

Outcomes included the total lidocaine dose administered (including all stages of Mohs surgery and the reconstruction) and patient comfort, which was measured subjectively with a 100-mm visual analog scale and objectively according to the volume of "rescue" lidocaine administered during the surgery. Analyses were based on 74 patients (with 83 tumors) in the 1.0% lidocaine group and 75 patients (with 85 tumors) in the 0.5% lidocaine group.

The mean total dose of lidocaine administered to patients in the 0.5% group was significantly lower, by 53%, than that administered to patients in the 1.0% group (139 mg vs. 297 mg). Mean scores for patient-rated pain (3.88 vs. 3.11 mm, respectively) or mean volume of rescue lidocaine administered (0.85 vs. 0.33 cc) did not differ significantly, Ms. Morganroth reported.

It appears that "0.5% lidocaine provides equivalent patient comfort at half the total dose of lidocaine as compared to 1.0% lidocaine," she said, while also acknowledging that the study did not measure blood levels of the drug.

"Our study demonstrates that 0.5% lidocaine decreases the risk of dose-dependent lidocaine toxicity without compromising patient comfort during Mohs surgery," said Ms. Morganroth, who reported having no conflicts of interest.

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

WILLIAMSBURG, VA. — Imiquimod can be a powerful tool for fighting in situ squamous cell carcinomas and superficial basal cell carcinomas, Dr. Roger Ceilley said.

"A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas," said Dr. Ceilley, at the annual meeting of the American Society for Mohs Surgery. "We may worry that when treating carcinoma in situ topically, that we are just treating the tip of the iceberg, but there are a few studies now that show even patients with an early invasive squamous cell carcinoma [SCC] treated three times a week for 12 weeks show clearing of the deeper component of the lesion."

Evidence is mounting for imiquimod's use on various sites of SCC in situ, including lesions on the anterior leg and penis, said Dr. Ceilley, a professor of dermatology at the University of Iowa, Iowa City. He noted seven case reports of imiquimod used successfully to treat penile lesions. The cream was applied anywhere from twice a week to every other day, depending on individual tolerance, for 8-16 weeks. "This is clearly an off-label use and you wouldn't want to do it without consulting a urologist but, with close management, this might be an alternative for an SCC that would otherwise result in a penectomy," he said.

Combined with 5-fluorouracil, imiquimod is especially effective for SCC lesions on the scalp, and dorsum of the hand—places that are often resistant to either treatment alone.

The cream also is approved for use in superficial basal cell carcinoma, where it has shown effectiveness. A 2004 placebo-controlled study found that up to 82% of patients had histologic clearance after a 6-week treatment cycle (J. Am. Acad. Dermatol. 2004;50:722-33). The study also found no significant difference in clearance rates among patients who used the cream five or seven times a week, lending support for the shorter treatment time. However, clearance was highly correlated with increased severity of erythema, erosion, and scabbing or crusting. The cosmetic outcomes were excellent.

For BCC, Dr. Ceilley said he prefers to use imiquimod prior to Mohs surgery, in conjunction with aggressive curettage and electrodesiccation. Treating for a few weeks preoperatively can reduce the defect, decrease the frequency of residual tumor, and improve cosmetic appearance.

"You can really define the lesions more carefully, minimizing the area of surgery you have to do," he said.

Evidence is mounting for the use of imiquimod in nodular BCC as well—especially in smaller, low-risk lesions or as adjunctive therapy. The original 2002 dosing study found a histologic clearance rate of up to 76%, with no significant difference between those who applied the medication daily for 12 or 16 weeks (Arch. Dermatol. 2002;138:1165-71), said Dr. Ceilley.

A more recent study found that while 70 of 90 patients (78%) had a complete clinical response, there was clinically visible tumor still present in 20 patients (22%). There was complete histopathologic clearance observed in 58 patients (64%), while residual tumor remained in 32 patients (36%). Efficacy was better in lesions smaller than 1 cm in diameter. The authors concluded that, since 17% of patients in the study with clinical clearance still had pathologic evidence of disease, excisional biopsy of the treated site is still indicated (J. Am. Acad. Dermatol. 2007;57:616-21).

Dr. Ceilley stated that he did not have any conflicts of interest to disclose.

'A number of studies have shown that imiquimod is up to 95% effective in clearing squamous cell carcinomas.' DR. CEILLEY

KYOTO, JAPAN — Topical calcineurin inhibitors should be used with caution when a diagnosis of atopic dermatitis is less than certain because they might accelerate progression of early-stage mycosis fungoides, often clinically indistinguishable from the atopic disorder.

"Biopsies should be obtained before using them on infiltrated facial lesions, which could be folliculotropic mycosis fungoides," Grace C. Sun advised at an international investigative dermatology meeting.

Because both the symptoms and skin biopsy findings are often nonspecific in early mycosis fungoides, many affected patients are misdiagnosed as having other skin diseases—particularly atopic dermatitis—for years before the proper diagnosis is eventually made. To examine the impact of topical calcineurin inhibitor (TCI) therapy in such patients, Ms. Sun of the M.D. Anderson Cancer Center, Houston, and coworkers conducted a retrospective study of 414 M.D. Anderson patients diagnosed with stage 1A or 1B mycosis fungoides during 2001-2007.

Of the 414 patients, 27 progressed beyond their initial T1/T2 skin stage within 6 years. In a multivariate regression analysis controlling for potential confounders, three factors emerged as being independently associated with reduced time to progression: the presence of large cell transformation on skin biopsy, which conferred a 3.3-fold increased risk of progression; prior pimecrolimus use, carrying a 5.4-fold increased risk; and a high serum lactate dehydrogenase concentration, which boosted the risk of early progression 23-fold.

Twenty-one of the 414 patients had a history of pimecrolimus therapy; 4 of those 21 progressed within 6 years. So did 1 of 10 patients who had been on tacrolimus and 18 of 250 with a history of topical corticosteroid therapy prior to being diagnosed with mycosis fungoides.

Of the four patients with a history of pimecrolimus use who progressed to a more advanced T stage within 6 years after diagnosis of mycosis fungoides, three had skin biopsies consistent with folliculotropic mycosis fungoides, a more aggressive variant. Three of the four patients developed tumors in areas where they had earlier applied pimecrolimus: on the head and face in two patients with folliculotropic mycosis fungoides, and on the antecubital fossa and hands in another patient.

The number of individuals with a history of tacrolimus therapy was too small to draw any conclusions regarding a possible relationship with time to progression, said Ms. Sun.

Seventeen percent of the 414 patients reported being initially misdiagnosed as having eczema. Six of these 69 patients progressed within 6 years, but none had previously used a TCI, she reported at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Both of the available TCIs—tacrolimus and pimecrolimus—are immunosuppressive, she said. The use of oral tacrolimus to prevent graft rejection in transplant recipients has been associated with increased risk of lymphoma; in animal models, systemic administration of either TCI has been found to increase the risk of lymphoma.

KYOTO, JAPAN — Topical calcineurin inhibitors should be used with caution when a diagnosis of atopic dermatitis is less than certain because they might accelerate progression of early-stage mycosis fungoides, often clinically indistinguishable from the atopic disorder.

"Biopsies should be obtained before using them on infiltrated facial lesions, which could be folliculotropic mycosis fungoides," Grace C. Sun advised at an international investigative dermatology meeting.

Because both the symptoms and skin biopsy findings are often nonspecific in early mycosis fungoides, many affected patients are misdiagnosed as having other skin diseases—particularly atopic dermatitis—for years before the proper diagnosis is eventually made. To examine the impact of topical calcineurin inhibitor (TCI) therapy in such patients, Ms. Sun of the M.D. Anderson Cancer Center, Houston, and coworkers conducted a retrospective study of 414 M.D. Anderson patients diagnosed with stage 1A or 1B mycosis fungoides during 2001-2007.

Of the 414 patients, 27 progressed beyond their initial T1/T2 skin stage within 6 years. In a multivariate regression analysis controlling for potential confounders, three factors emerged as being independently associated with reduced time to progression: the presence of large cell transformation on skin biopsy, which conferred a 3.3-fold increased risk of progression; prior pimecrolimus use, carrying a 5.4-fold increased risk; and a high serum lactate dehydrogenase concentration, which boosted the risk of early progression 23-fold.

Twenty-one of the 414 patients had a history of pimecrolimus therapy; 4 of those 21 progressed within 6 years. So did 1 of 10 patients who had been on tacrolimus and 18 of 250 with a history of topical corticosteroid therapy prior to being diagnosed with mycosis fungoides.

Of the four patients with a history of pimecrolimus use who progressed to a more advanced T stage within 6 years after diagnosis of mycosis fungoides, three had skin biopsies consistent with folliculotropic mycosis fungoides, a more aggressive variant. Three of the four patients developed tumors in areas where they had earlier applied pimecrolimus: on the head and face in two patients with folliculotropic mycosis fungoides, and on the antecubital fossa and hands in another patient.

The number of individuals with a history of tacrolimus therapy was too small to draw any conclusions regarding a possible relationship with time to progression, said Ms. Sun.

Seventeen percent of the 414 patients reported being initially misdiagnosed as having eczema. Six of these 69 patients progressed within 6 years, but none had previously used a TCI, she reported at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Both of the available TCIs—tacrolimus and pimecrolimus—are immunosuppressive, she said. The use of oral tacrolimus to prevent graft rejection in transplant recipients has been associated with increased risk of lymphoma; in animal models, systemic administration of either TCI has been found to increase the risk of lymphoma.

KYOTO, JAPAN — Topical calcineurin inhibitors should be used with caution when a diagnosis of atopic dermatitis is less than certain because they might accelerate progression of early-stage mycosis fungoides, often clinically indistinguishable from the atopic disorder.

"Biopsies should be obtained before using them on infiltrated facial lesions, which could be folliculotropic mycosis fungoides," Grace C. Sun advised at an international investigative dermatology meeting.

Because both the symptoms and skin biopsy findings are often nonspecific in early mycosis fungoides, many affected patients are misdiagnosed as having other skin diseases—particularly atopic dermatitis—for years before the proper diagnosis is eventually made. To examine the impact of topical calcineurin inhibitor (TCI) therapy in such patients, Ms. Sun of the M.D. Anderson Cancer Center, Houston, and coworkers conducted a retrospective study of 414 M.D. Anderson patients diagnosed with stage 1A or 1B mycosis fungoides during 2001-2007.

Of the 414 patients, 27 progressed beyond their initial T1/T2 skin stage within 6 years. In a multivariate regression analysis controlling for potential confounders, three factors emerged as being independently associated with reduced time to progression: the presence of large cell transformation on skin biopsy, which conferred a 3.3-fold increased risk of progression; prior pimecrolimus use, carrying a 5.4-fold increased risk; and a high serum lactate dehydrogenase concentration, which boosted the risk of early progression 23-fold.

Twenty-one of the 414 patients had a history of pimecrolimus therapy; 4 of those 21 progressed within 6 years. So did 1 of 10 patients who had been on tacrolimus and 18 of 250 with a history of topical corticosteroid therapy prior to being diagnosed with mycosis fungoides.

Of the four patients with a history of pimecrolimus use who progressed to a more advanced T stage within 6 years after diagnosis of mycosis fungoides, three had skin biopsies consistent with folliculotropic mycosis fungoides, a more aggressive variant. Three of the four patients developed tumors in areas where they had earlier applied pimecrolimus: on the head and face in two patients with folliculotropic mycosis fungoides, and on the antecubital fossa and hands in another patient.

The number of individuals with a history of tacrolimus therapy was too small to draw any conclusions regarding a possible relationship with time to progression, said Ms. Sun.

Seventeen percent of the 414 patients reported being initially misdiagnosed as having eczema. Six of these 69 patients progressed within 6 years, but none had previously used a TCI, she reported at a meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Both of the available TCIs—tacrolimus and pimecrolimus—are immunosuppressive, she said. The use of oral tacrolimus to prevent graft rejection in transplant recipients has been associated with increased risk of lymphoma; in animal models, systemic administration of either TCI has been found to increase the risk of lymphoma.

The Skin Cancer Foundation's brochure entitled "The ABCDEs of Melanoma" is now available in both English and Spanish. The foldout helps patients to identify the most important differences between common moles and melanomas: Asymmetry, Border irregularity, Color variations, and large Diameter and Evolving. To order copies, contact the foundation at 800-754-6490.

The Skin Cancer Foundation's brochure entitled "The ABCDEs of Melanoma" is now available in both English and Spanish. The foldout helps patients to identify the most important differences between common moles and melanomas: Asymmetry, Border irregularity, Color variations, and large Diameter and Evolving. To order copies, contact the foundation at 800-754-6490.

The Skin Cancer Foundation's brochure entitled "The ABCDEs of Melanoma" is now available in both English and Spanish. The foldout helps patients to identify the most important differences between common moles and melanomas: Asymmetry, Border irregularity, Color variations, and large Diameter and Evolving. To order copies, contact the foundation at 800-754-6490.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.

Prolonged therapy with pegylated interferon has been found to improve recurrence-free survival in patients with excised stage III melanoma in a randomized phase III trial.

In contrast, survival free of distant metastases was numerically but not statistically significantly better with adjuvant pegylated interferon, and the treatment had no apparent effect on overall survival, Dr. Alexander M. M. Eggermont and his associates reported in the European Organisation for Research and Treatment of Cancer (EORTC) trial 18991 (Lancet 2008;372:117-26).

In an editorial comment that accompanied the report, Dr. Vernon K. Sondak and Dr. Lawrence E. Flaherty wrote that "many patients with melanoma are willing to accept significant toxicity in exchange for a modest improvement in recurrence-free survival, even in the absence of an overall survival effect," (Lancet 2008;372:89-90).

It remains to be seen, however, whether such patients and their physicians will accept 5 years of pegylated interferon treatment "for an absolute benefit in recurrence-free survival of about 6% at 4 years," they noted.

Dr. Eggermont and his colleagues compared the therapy with observation alone in a randomized controlled trial involving 1,256 patients treated at 99 medical centers in 17 countries. All patients had undergone complete excision of stage III melanoma and complete regional lymphadenectomy.

The study was funded by Schering-Plough Research International.

The two study groups were well matched according to disease substage, number of involved lymph nodes, thickness of the primary tumor, and ulceration of the primary tumor. Patients who took interferon received high-dose induction therapy for 8 weeks, followed by once-weekly self-administered subcutaneous injections for an intended duration of 5 years, said Dr. Eggermont, of Erasmus University, Rotterdam, the Netherlands, and his associates.

After a median of 4 years of follow-up, significantly fewer recurrences had developed in the interferon group than in the observation group, with a 6.7% absolute difference in estimated rates of recurrence-free survival. The therapy's benefit was seen early in the course of treatment and remained at a consistent level throughout the study, the investigators said.

However, there was no difference in overall survival between patients who took pegylated interferon and those who did not.

The drug was most effective in patients who had microscopic rather than palpable nodal disease, patients whose involvement was limited to one lymph node, and in patients with ulcerated rather than nonulcerated tumors. These groups accounted for approximately 40% of the treated patients.

One-third of the study subjects who took interferon discontinued the drug because of toxicity. The most common adverse effects were fatigue and depression, which were reported in 25% and 16% of patients, respectively. Anorexia, liver function abnormalities, myalgia, headache, nausea, and fever also were reported.

In their editorial comment, Dr. Sondak of H. Lee Moffitt Cancer Center, Tampa, and Dr. Flaherty of Karmanos Cancer Institute, Detroit, said that a 4-year follow-up "is too short for final conclusions." Further follow-up and more clinical trials are needed. However, they added, "for the large group of patients with melanoma found in their sentinel node, we believe this regimen will be an attractive alternative to high-dose interferon."

Dr. Eggermont, Dr. Sondak, and Dr. Flaherty have all been paid consultants for Schering-Plough.