Melanoma

CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.

A randomized multicenter phase II study is being planned to compare the cetuximab and TPF combination with the M.D. Anderson Cancer Center induction regimen consisting of carboplatin, paclitaxel, and cetiuximab, Dr. Haddad said.

The study was supported by Bristol-Myers Squibb. Dr. Haddad disclosed receiving honoraria and research support from the company, and honoraria from Sanofi-Aventis and Imclone Systems.

CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.

A randomized multicenter phase II study is being planned to compare the cetuximab and TPF combination with the M.D. Anderson Cancer Center induction regimen consisting of carboplatin, paclitaxel, and cetiuximab, Dr. Haddad said.

The study was supported by Bristol-Myers Squibb. Dr. Haddad disclosed receiving honoraria and research support from the company, and honoraria from Sanofi-Aventis and Imclone Systems.

CHICAGO — Cetuximab can be added safely and apparently to good effect when giving a standard induction regimen to patients with newly diagnosed, locally advanced head and neck cancer, reported investigators at the annual meeting of the American Society of Clinical Oncology.

In a phase I study looking at the addition of cetuximab (Erbitux) to induction chemotherapy with docetaxel (Taxotere), cisplatin, and 5-fluorouracil (the TPF regimen), 14 of 19 treated patients had a complete clinical response, 5 had a partial clinical response, and all 19 had a partial radiographic response, reported Dr. Robert I. Haddad, who is a clinical investigator in the Head and Neck Cancer Center at the Dana Farber Cancer Institute in Boston.

"The preliminary efficacy data [are] encouraging in this patient population with fairly advanced presentation," Dr. Haddad said.

The TPF regimen is both a new standard for induction chemotherapy in patients with previously untreated squamous cell carcinomas of the head and neck, and a platform for testing new agents such as cetuximab, which has been shown to have efficacy in head and neck cancer as a single agent and in combination with radiation therapy and cistplatin/5-fluorouracil (PF) chemotherapy, Dr. Haddad said.

He and his colleagues conducted a phase I study of the maximum tolerated dose of 5-fluorouracil (5-FU) in the TPF regimen when cetuximab was added. Secondary goals of the study included a toxicity assessment and response rates.

They enrolled 28 patients with biopsy-proven squamous cell carcinoma of the head and neck, with primary tumor sites in the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx. Patients with unknown primary site squamous cell carcinomas were also eligible.

The patients had to have stage III or IV disease with no evidence of distant metastases, and they had to have no prior chemotherapy, radiation therapy, or surgery, measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors). In addition, patients needed to have good Eastern Cooperative Oncology Group performance status (0 or 1), and normal hematologic, renal, and liver function.

Patients received 400 mg/m

The treatment plan called for three cycles of induction chemotherapy, with TPF every 21 days, plus weekly cetuximab in doses of 250 mg/m

At the end of induction, restaging was performed and then patients underwent definitive chemoradiotherapy with a platinum-based regimen according to the institution's standard.

One of the patients withdrew consent before toxicity could be assessed, leaving 27 available for the analysis. Of these patients, 19 had completed chemoradiotherapy at the time Dr. Haddad presented the data.

There were no dose-limiting toxicities after the first cycle of cetuximab/TPF with 5-FU at 750 or 850 mg/m

But in that expanded cohort, there were two cases of gastrointestinal bleeding and one of febrile neutropenia, causing the investigators to reconsider 5-FU dosing, and they instead settled on 850 mg as the maximum tolerated dose. Of the 10 patients planned for enrollment in the expanded cohort at this dose, nine had enrolled at the time of the analysis. Only one dose-limiting toxicity was reported: mucositis.

Among the 12 patients in total enrolled at the 850-mg dose (3 from the original cohort, plus 9 additionally enrolled), there were four cases of grade 4 neutropenia and one of grade 4 diarrhea. Grade 3 events include three cases of neutropenia, two of febrile neutropenia, one mucositis (dose limiting), one fatigue, and one syncope. Skin toxicities included acneiform rash (seven grade 2 and one grade 3), and four cases of grade 2 nail fissuring and/or paronychial infection.

At the time of the data presentation, 19 of 27 patients had completed chemoradiotherapy with a platinum-based agent, and 8 remained on treatment. All but one of the patients received 70-Gy radiation over 7 weeks; the remaining patients received 59 Gy over 10 weeks.

An analysis of the best overall response showed a clinical complete response in 14 patients, and partial response in 5. Radiographic evaluation at the end of induction but before radiation showed a partial response in all 19 patients.

"All of these patients had still-persistent abnormalities on CT or PET," Dr. Haddad said. "Keep in mind these patients have fairly advanced nodal presentations, and often the CT scan or imaging is not normalized for these patients."

Among the 13 patients who underwent primary site biopsy after induction, 11 had pathologic complete response, and 2 had a partial response.

All patients were alive at 6-month follow-up; one patient with a stage T4 N2b cancer of the base of the tongue had local/regional recurrence and is currently on palliative chemotherapy. Two patients had neck dissections performed after chemoradiotherapy, and neither had pathologic evidence of residual cancer in the surgical specimen.

A randomized multicenter phase II study is being planned to compare the cetuximab and TPF combination with the M.D. Anderson Cancer Center induction regimen consisting of carboplatin, paclitaxel, and cetiuximab, Dr. Haddad said.

The study was supported by Bristol-Myers Squibb. Dr. Haddad disclosed receiving honoraria and research support from the company, and honoraria from Sanofi-Aventis and Imclone Systems.

KYOTO, JAPAN — Prophylactic oral N-acetylcysteine has shown early promise as a novel melanoma chemoprevention strategy, said Dr. Douglas Grossman.

Taking N-acetylcysteine (NAC) episodically in anticipation of a day at the beach or before other heavy sun exposure may prevent UV-induced oxidative damage to melanocytic nevi, thereby reducing the long-term risk of malignant transformation, explained Dr. Grossman at an international investigative dermatology meeting.

The drug targets oxidative damage, a specific oncogenic pathway that is induced by UV irradiation. NAC has the ability to sidestep the inherent drawbacks of daily chemopreventive therapy, including compliance problems and drug side effects, said Dr. Grossman of the University of Utah, Salt Lake City. And sunscreens alone seem inadequate for melanoma prevention; in fact, some studies have shown a higher incidence of melanoma in sunscreen users, he said.

NAC is an ideal drug to study for chemoprevention. It has a relatively short serum half-life of 5.5 hours. It is rapidly metabolized to cysteine and converted to glutathione, a potent antioxidant that is depleted by UV.

"NAC is well characterized, cheap, cell-permeable, and has a safety record already demonstrated in humans," the dermatologist noted.

Other investigators have already shown that NAC is useful in preventing oxidative damage in the skin. It is FDA approved for the treatment of toxicity from acute acetaminophen overdose. More recently, it has been used to prevent intravenous contrast-induced nephropathy.

In mouse studies, Dr. Grossman and coworkers have demonstrated that NAC prevents UV-induced formation of the carcinogen 8-oxoguanine and delays onset of UV-induced melanoma (Clin. Cancer Res. 2007;13:5952-8).

In Kyoto, he presented the first clinical study of NAC for melanoma chemoprevention. It involved eight patients who underwent biopsy of a nevus prior to administration of a single 1,200-mg oral dose of NAC. Three hours after NAC administration, a second nevus was removed. The nevi were then irradiated ex vivo with UV at 4,000 J/m

When the nevi were analyzed 24 hours post UV exposure, the control samples showed roughly a 50% reduction in glutathione levels and an increase in 8-oxoguanine, compared with baseline. In contrast, the nevi exposed in vivo to NAC showed no depletion of glutathione and no rise in 8-oxoguanine in three of eight patients.

In hindsight, Dr. Grossman said, the analysis probably should have been done 48 hours post UV exposure rather than at 24 hours. The earlier mouse studies suggested oxidative stress and damage were at their maximum levels at the 48-hour time point.

"We see this as a pilot study in which we had some moderate success in a small number of patients. We're now poised to do a second trial using the 48-hour time point, which we think will be much more robust," Dr. Grossman said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Also planned are clinical trials looking at NAC's protective effect in response to UV irradiation in vivo. The possibility that NAC is protective when taken following UV exposure is also worthy of investigation, he added.

The optimal dose of NAC for chemoprevention remains unknown. The 1,200-mg dose used in this study was well tolerated. "Higher doses are probably safe, but we don't know if they'd confer greater protection or not, so we'll probably stick with 1,200 mg," said Dr. Grossman.

His study was funded by the university's Huntsman Cancer Institute.

KYOTO, JAPAN — Prophylactic oral N-acetylcysteine has shown early promise as a novel melanoma chemoprevention strategy, said Dr. Douglas Grossman.

Taking N-acetylcysteine (NAC) episodically in anticipation of a day at the beach or before other heavy sun exposure may prevent UV-induced oxidative damage to melanocytic nevi, thereby reducing the long-term risk of malignant transformation, explained Dr. Grossman at an international investigative dermatology meeting.

The drug targets oxidative damage, a specific oncogenic pathway that is induced by UV irradiation. NAC has the ability to sidestep the inherent drawbacks of daily chemopreventive therapy, including compliance problems and drug side effects, said Dr. Grossman of the University of Utah, Salt Lake City. And sunscreens alone seem inadequate for melanoma prevention; in fact, some studies have shown a higher incidence of melanoma in sunscreen users, he said.

NAC is an ideal drug to study for chemoprevention. It has a relatively short serum half-life of 5.5 hours. It is rapidly metabolized to cysteine and converted to glutathione, a potent antioxidant that is depleted by UV.

"NAC is well characterized, cheap, cell-permeable, and has a safety record already demonstrated in humans," the dermatologist noted.

Other investigators have already shown that NAC is useful in preventing oxidative damage in the skin. It is FDA approved for the treatment of toxicity from acute acetaminophen overdose. More recently, it has been used to prevent intravenous contrast-induced nephropathy.

In mouse studies, Dr. Grossman and coworkers have demonstrated that NAC prevents UV-induced formation of the carcinogen 8-oxoguanine and delays onset of UV-induced melanoma (Clin. Cancer Res. 2007;13:5952-8).

In Kyoto, he presented the first clinical study of NAC for melanoma chemoprevention. It involved eight patients who underwent biopsy of a nevus prior to administration of a single 1,200-mg oral dose of NAC. Three hours after NAC administration, a second nevus was removed. The nevi were then irradiated ex vivo with UV at 4,000 J/m

When the nevi were analyzed 24 hours post UV exposure, the control samples showed roughly a 50% reduction in glutathione levels and an increase in 8-oxoguanine, compared with baseline. In contrast, the nevi exposed in vivo to NAC showed no depletion of glutathione and no rise in 8-oxoguanine in three of eight patients.

In hindsight, Dr. Grossman said, the analysis probably should have been done 48 hours post UV exposure rather than at 24 hours. The earlier mouse studies suggested oxidative stress and damage were at their maximum levels at the 48-hour time point.

"We see this as a pilot study in which we had some moderate success in a small number of patients. We're now poised to do a second trial using the 48-hour time point, which we think will be much more robust," Dr. Grossman said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Also planned are clinical trials looking at NAC's protective effect in response to UV irradiation in vivo. The possibility that NAC is protective when taken following UV exposure is also worthy of investigation, he added.

The optimal dose of NAC for chemoprevention remains unknown. The 1,200-mg dose used in this study was well tolerated. "Higher doses are probably safe, but we don't know if they'd confer greater protection or not, so we'll probably stick with 1,200 mg," said Dr. Grossman.

His study was funded by the university's Huntsman Cancer Institute.

KYOTO, JAPAN — Prophylactic oral N-acetylcysteine has shown early promise as a novel melanoma chemoprevention strategy, said Dr. Douglas Grossman.

Taking N-acetylcysteine (NAC) episodically in anticipation of a day at the beach or before other heavy sun exposure may prevent UV-induced oxidative damage to melanocytic nevi, thereby reducing the long-term risk of malignant transformation, explained Dr. Grossman at an international investigative dermatology meeting.

The drug targets oxidative damage, a specific oncogenic pathway that is induced by UV irradiation. NAC has the ability to sidestep the inherent drawbacks of daily chemopreventive therapy, including compliance problems and drug side effects, said Dr. Grossman of the University of Utah, Salt Lake City. And sunscreens alone seem inadequate for melanoma prevention; in fact, some studies have shown a higher incidence of melanoma in sunscreen users, he said.

NAC is an ideal drug to study for chemoprevention. It has a relatively short serum half-life of 5.5 hours. It is rapidly metabolized to cysteine and converted to glutathione, a potent antioxidant that is depleted by UV.

"NAC is well characterized, cheap, cell-permeable, and has a safety record already demonstrated in humans," the dermatologist noted.

Other investigators have already shown that NAC is useful in preventing oxidative damage in the skin. It is FDA approved for the treatment of toxicity from acute acetaminophen overdose. More recently, it has been used to prevent intravenous contrast-induced nephropathy.

In mouse studies, Dr. Grossman and coworkers have demonstrated that NAC prevents UV-induced formation of the carcinogen 8-oxoguanine and delays onset of UV-induced melanoma (Clin. Cancer Res. 2007;13:5952-8).

In Kyoto, he presented the first clinical study of NAC for melanoma chemoprevention. It involved eight patients who underwent biopsy of a nevus prior to administration of a single 1,200-mg oral dose of NAC. Three hours after NAC administration, a second nevus was removed. The nevi were then irradiated ex vivo with UV at 4,000 J/m

When the nevi were analyzed 24 hours post UV exposure, the control samples showed roughly a 50% reduction in glutathione levels and an increase in 8-oxoguanine, compared with baseline. In contrast, the nevi exposed in vivo to NAC showed no depletion of glutathione and no rise in 8-oxoguanine in three of eight patients.

In hindsight, Dr. Grossman said, the analysis probably should have been done 48 hours post UV exposure rather than at 24 hours. The earlier mouse studies suggested oxidative stress and damage were at their maximum levels at the 48-hour time point.

"We see this as a pilot study in which we had some moderate success in a small number of patients. We're now poised to do a second trial using the 48-hour time point, which we think will be much more robust," Dr. Grossman said at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

Also planned are clinical trials looking at NAC's protective effect in response to UV irradiation in vivo. The possibility that NAC is protective when taken following UV exposure is also worthy of investigation, he added.

The optimal dose of NAC for chemoprevention remains unknown. The 1,200-mg dose used in this study was well tolerated. "Higher doses are probably safe, but we don't know if they'd confer greater protection or not, so we'll probably stick with 1,200 mg," said Dr. Grossman.

His study was funded by the university's Huntsman Cancer Institute.

CHICAGO — Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.

The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.

The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.

No association was found for the other nine SNPs.

"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.

"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.

The researchers reported that they had no conflicts of interest.

CHICAGO — Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.

The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.

The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.

No association was found for the other nine SNPs.

"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.

"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.

The researchers reported that they had no conflicts of interest.

CHICAGO — Single nucleotide polymorphisms in DNA repair genes may help predict not only metastatic capacity but also survival in patients with primary cutaneous melanoma, according to a 400-patient study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

Dr. Dirk Schadendorf of the skin cancer unit of the German Cancer Research Center in Heidelberg, Germany, and his coauthors genotyped 13 single-nucleotide polymorphisms (SNPs) from eight different DNA repair genes in 400 cutaneous melanoma patients. Average patient follow-up was 3.7 years, with 46% of patients having metastasis during that period.

The researchers found that melanoma patients with the AA genotype for the R399Q XRCC1 polymorphism showed better overall survival (hazard ratio, 0.32; P = .03) and metastasis-free survival (HR, 0.40; P = .007) compared with patients who were heterozygous and homozygous (GG). However, survival following metastasis was comparable between the groups.

The study also found that patients with AG and GG genotypes for the −1842 XRCC3 polymorphism (1843bp 5′ of the start codon in the promoter region) showed decreased survival following metastasis, although these differences in mortality after metastasis were significant only for the AG genotype (HR, 1.99; P = .003 [for AG]; HR, 1.53; P = .5 [for GG]) as was mortality overall (HR, 1.68; P = .02 for AG), compared with patients who were homozygous (AA). Metastasis-free survival did not differ between the groups.

No association was found for the other nine SNPs.

"Genetic stability, at least during a specific phase of tumor development, appears to be necessary for a malignant melanoma cell to give rise to metastasis. Accordingly, impaired repair functionality could account for reduced metastatic capacity, better metastasis-free survival, and overall survival as observed in patients homozygous for the variant allele for the R399Q XRCC1 and the K751Q ERCC2 polymorphisms in our study," the researchers wrote.

"Our data support the concept that overall survival is a sum of factors influencing time from diagnosis of the primary [cancer] to first relapse and factors contributing independently after tumor progression to final outcome," they wrote.

The researchers reported that they had no conflicts of interest.

CHICAGO — KIT gene mutations that are susceptible to imatinib occur in some acral and mucosal melanomas, opening up new therapeutic options for patients with melanoma, according to a study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

KIT mutations were found in 23% of acral melanomas and 16% of mucosal melanomas, reported Dr. Michael C. Heinrich, professor of medicine at the Oregon Health and Science University, Portland, and his colleagues. The mutation frequency was greater among tumors of the anorectum, vulva, and vagina (44%) than among the head and neck (8%).

In contrast, KIT mutations accounted for only 2% of cutaneous melanomas and for 8% of conjunctival melanomas. No mutations were found in an additional 60 choroidal melanomas.

"Based on our study, approximately 40%-50% of all types of melanoma have an oncogenic mutation that could be treated with drugs that are or will be in clinical studies within the next 18 months," Dr. Heinrich said in an interview.

For the study, DNA from archival melanomas was amplified by polymerase-chain reaction (PCR) and the products were screened for mutations in KIT exons 11, 13, 17 (n = 189), BRAF exon 15 (n = 116), and NRAS exons 1 and 2 (n = 117). Mutations were confirmed by direct sequencing.

In addition, immunohistochemistry for CD117 (KIT) was performed on a subset of cases. Lastly, the researchers assessed increases in KIT copy number in specific melanoma subtypes using quantitative real-time PCR.

Six of seven KIT mutations identified were of the type predicted to be sensitive to imatinib (Gleevec). KIT mutations did not overlap with NRAS mutations—which were also common in acral and mucosal tumors—or with BRAF mutations, which were absent in mucosal tumors.

"In the not too distant future, we envision that advanced melanoma tumors would be routinely tested for these types of mutations and the results used to make clinical decisions about the best medical treatment. This would be similar to the existing breast cancer model where ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2] testing are routine pathology tests that are used to individualize treatment programs," said Dr. Heinrich.

Imatinib is indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and KIT-positive gastrointestinal stromal tumors.

Using a PCR-based assay, the researchers found that KIT was increased in acral and mucosal melanoma cases, though most of the tumors with increased KIT did not have a mutation. Extra KIT copies were not as common in cutaneous and conjunctival tumors. KIT (CD-117) expression was detected in 39% of 105 tumors; however, there was no correlation between CD-117 staining and tumor genotype. KIT mutations of the type known to be sensitive to imatinib do not necessarily correlate with either KIT copy number or CD-117 expression, the researchers noted.

The study was prompted by a recent rectal melanoma case in which a patient with a KIT mutation had a dramatic response to imatinib.

Dr. Heinrich reported that he has received research funding from Novartis and Pfizer Inc., is a consultant for Novartis, and has equity interest in MolecularMD. One of his coauthors has received research funding from Novartis and Pfizer and is a consultant for Novartis.

CHICAGO — KIT gene mutations that are susceptible to imatinib occur in some acral and mucosal melanomas, opening up new therapeutic options for patients with melanoma, according to a study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

KIT mutations were found in 23% of acral melanomas and 16% of mucosal melanomas, reported Dr. Michael C. Heinrich, professor of medicine at the Oregon Health and Science University, Portland, and his colleagues. The mutation frequency was greater among tumors of the anorectum, vulva, and vagina (44%) than among the head and neck (8%).

In contrast, KIT mutations accounted for only 2% of cutaneous melanomas and for 8% of conjunctival melanomas. No mutations were found in an additional 60 choroidal melanomas.

"Based on our study, approximately 40%-50% of all types of melanoma have an oncogenic mutation that could be treated with drugs that are or will be in clinical studies within the next 18 months," Dr. Heinrich said in an interview.

For the study, DNA from archival melanomas was amplified by polymerase-chain reaction (PCR) and the products were screened for mutations in KIT exons 11, 13, 17 (n = 189), BRAF exon 15 (n = 116), and NRAS exons 1 and 2 (n = 117). Mutations were confirmed by direct sequencing.

In addition, immunohistochemistry for CD117 (KIT) was performed on a subset of cases. Lastly, the researchers assessed increases in KIT copy number in specific melanoma subtypes using quantitative real-time PCR.

Six of seven KIT mutations identified were of the type predicted to be sensitive to imatinib (Gleevec). KIT mutations did not overlap with NRAS mutations—which were also common in acral and mucosal tumors—or with BRAF mutations, which were absent in mucosal tumors.

"In the not too distant future, we envision that advanced melanoma tumors would be routinely tested for these types of mutations and the results used to make clinical decisions about the best medical treatment. This would be similar to the existing breast cancer model where ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2] testing are routine pathology tests that are used to individualize treatment programs," said Dr. Heinrich.

Imatinib is indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and KIT-positive gastrointestinal stromal tumors.

Using a PCR-based assay, the researchers found that KIT was increased in acral and mucosal melanoma cases, though most of the tumors with increased KIT did not have a mutation. Extra KIT copies were not as common in cutaneous and conjunctival tumors. KIT (CD-117) expression was detected in 39% of 105 tumors; however, there was no correlation between CD-117 staining and tumor genotype. KIT mutations of the type known to be sensitive to imatinib do not necessarily correlate with either KIT copy number or CD-117 expression, the researchers noted.

The study was prompted by a recent rectal melanoma case in which a patient with a KIT mutation had a dramatic response to imatinib.

Dr. Heinrich reported that he has received research funding from Novartis and Pfizer Inc., is a consultant for Novartis, and has equity interest in MolecularMD. One of his coauthors has received research funding from Novartis and Pfizer and is a consultant for Novartis.

CHICAGO — KIT gene mutations that are susceptible to imatinib occur in some acral and mucosal melanomas, opening up new therapeutic options for patients with melanoma, according to a study presented as a poster at the annual meeting of the American Society of Clinical Oncology.

KIT mutations were found in 23% of acral melanomas and 16% of mucosal melanomas, reported Dr. Michael C. Heinrich, professor of medicine at the Oregon Health and Science University, Portland, and his colleagues. The mutation frequency was greater among tumors of the anorectum, vulva, and vagina (44%) than among the head and neck (8%).

In contrast, KIT mutations accounted for only 2% of cutaneous melanomas and for 8% of conjunctival melanomas. No mutations were found in an additional 60 choroidal melanomas.

"Based on our study, approximately 40%-50% of all types of melanoma have an oncogenic mutation that could be treated with drugs that are or will be in clinical studies within the next 18 months," Dr. Heinrich said in an interview.

For the study, DNA from archival melanomas was amplified by polymerase-chain reaction (PCR) and the products were screened for mutations in KIT exons 11, 13, 17 (n = 189), BRAF exon 15 (n = 116), and NRAS exons 1 and 2 (n = 117). Mutations were confirmed by direct sequencing.

In addition, immunohistochemistry for CD117 (KIT) was performed on a subset of cases. Lastly, the researchers assessed increases in KIT copy number in specific melanoma subtypes using quantitative real-time PCR.

Six of seven KIT mutations identified were of the type predicted to be sensitive to imatinib (Gleevec). KIT mutations did not overlap with NRAS mutations—which were also common in acral and mucosal tumors—or with BRAF mutations, which were absent in mucosal tumors.

"In the not too distant future, we envision that advanced melanoma tumors would be routinely tested for these types of mutations and the results used to make clinical decisions about the best medical treatment. This would be similar to the existing breast cancer model where ER [estrogen receptor] and HER2 [human epidermal growth factor receptor 2] testing are routine pathology tests that are used to individualize treatment programs," said Dr. Heinrich.

Imatinib is indicated for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, Philadelphia chromosome-positive acute lymphoblastic leukemia, myelodysplastic/myeloproliferative diseases, hypereosinophilic syndrome and/or chronic eosinophilic leukemia, dermatofibrosarcoma protuberans, and KIT-positive gastrointestinal stromal tumors.

Using a PCR-based assay, the researchers found that KIT was increased in acral and mucosal melanoma cases, though most of the tumors with increased KIT did not have a mutation. Extra KIT copies were not as common in cutaneous and conjunctival tumors. KIT (CD-117) expression was detected in 39% of 105 tumors; however, there was no correlation between CD-117 staining and tumor genotype. KIT mutations of the type known to be sensitive to imatinib do not necessarily correlate with either KIT copy number or CD-117 expression, the researchers noted.

The study was prompted by a recent rectal melanoma case in which a patient with a KIT mutation had a dramatic response to imatinib.

Dr. Heinrich reported that he has received research funding from Novartis and Pfizer Inc., is a consultant for Novartis, and has equity interest in MolecularMD. One of his coauthors has received research funding from Novartis and Pfizer and is a consultant for Novartis.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

KYOTO, JAPAN — The use of sunless tanning products by women in the United States is on the rise, with the most cited reason by users being the topical products' safety as an alternative to sunbathing and tanning beds.

This is a most welcome trend. Increased public acceptance of sunless tanning products (STPs) holds the potential to cause a substantial reduction in skin cancer rates, Mary Jayne McIlwaine reported at an international investigative dermatology meeting.

"Despite the growing knowledge of the danger of sun exposure and UV tanning, our results suggest that a large proportion of the population still believes tanning is desirable and attractive. Until public opinion changes, it's important to provide the public with suitable ways to tan their skin without the dangers of UV exposure—such as STPs," she added at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

She surveyed 415 women, average age 28 years, regarding their tanning behaviors and beliefs. The women were queried in gyms, swimming pools, and university sororities and dining halls.

Forty-eight percent of respondents reported using STPs at least once in the past year. "That's a much higher percentage than in previous published studies. This suggests STP use may be increasing," according to Ms. McIlwaine, who is a medical student at Emory University in Atlanta.

Encouragingly, 35% of the STP users indicated they employed these "tan-in-a-can" products as at least a partial replacement for sunbathing, and 25% reported using STPs in lieu of tanning beds.

STPs appear to be more popular with younger women. Fifty-four percent of 18-to 25-year-olds reported using them within the past year, compared with 41% of those aged 26-40 years and 40% of respondents over the age of 40.

Only 14% of women with brown or black skin reported STP use, compared with 56% of those with very white/freckled skin and 54% with white/olive skin.

The survey results suggest that, in spite of the growing awareness of the dangers of UV tanning, core ideas regarding the desirability of the tanned look remain largely unchanged. Ninety-three percent of the survey respondents indicated they believe tanned skin is more attractive than untanned skin. Seventy-nine percent said that they feel better about themselves when they have a tan. Seventy-one percent of subjects reported sunbathing at least once during the past year, and 26% used a tanning bed.

Most STPs contain dihydroacetone, which reacts with amino acids in the stratum corneum to produce a temporary brown hue.

Respondents' top reasons for not using STPs were dislike of product color and streakiness. Thus, further technical improvements in product quality might be important in achieving greater public acceptance and more widespread use of STPs as a tool for skin cancer prevention, Ms. McIlwaine concluded.

"Tan-in-a-can" products appear to be more popular with younger women. Shane Wake

KYOTO, JAPAN — The use of sunless tanning products by women in the United States is on the rise, with the most cited reason by users being the topical products' safety as an alternative to sunbathing and tanning beds.

This is a most welcome trend. Increased public acceptance of sunless tanning products (STPs) holds the potential to cause a substantial reduction in skin cancer rates, Mary Jayne McIlwaine reported at an international investigative dermatology meeting.

"Despite the growing knowledge of the danger of sun exposure and UV tanning, our results suggest that a large proportion of the population still believes tanning is desirable and attractive. Until public opinion changes, it's important to provide the public with suitable ways to tan their skin without the dangers of UV exposure—such as STPs," she added at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

She surveyed 415 women, average age 28 years, regarding their tanning behaviors and beliefs. The women were queried in gyms, swimming pools, and university sororities and dining halls.

Forty-eight percent of respondents reported using STPs at least once in the past year. "That's a much higher percentage than in previous published studies. This suggests STP use may be increasing," according to Ms. McIlwaine, who is a medical student at Emory University in Atlanta.

Encouragingly, 35% of the STP users indicated they employed these "tan-in-a-can" products as at least a partial replacement for sunbathing, and 25% reported using STPs in lieu of tanning beds.

STPs appear to be more popular with younger women. Fifty-four percent of 18-to 25-year-olds reported using them within the past year, compared with 41% of those aged 26-40 years and 40% of respondents over the age of 40.

Only 14% of women with brown or black skin reported STP use, compared with 56% of those with very white/freckled skin and 54% with white/olive skin.

The survey results suggest that, in spite of the growing awareness of the dangers of UV tanning, core ideas regarding the desirability of the tanned look remain largely unchanged. Ninety-three percent of the survey respondents indicated they believe tanned skin is more attractive than untanned skin. Seventy-nine percent said that they feel better about themselves when they have a tan. Seventy-one percent of subjects reported sunbathing at least once during the past year, and 26% used a tanning bed.

Most STPs contain dihydroacetone, which reacts with amino acids in the stratum corneum to produce a temporary brown hue.

Respondents' top reasons for not using STPs were dislike of product color and streakiness. Thus, further technical improvements in product quality might be important in achieving greater public acceptance and more widespread use of STPs as a tool for skin cancer prevention, Ms. McIlwaine concluded.

"Tan-in-a-can" products appear to be more popular with younger women. Shane Wake

KYOTO, JAPAN — The use of sunless tanning products by women in the United States is on the rise, with the most cited reason by users being the topical products' safety as an alternative to sunbathing and tanning beds.

This is a most welcome trend. Increased public acceptance of sunless tanning products (STPs) holds the potential to cause a substantial reduction in skin cancer rates, Mary Jayne McIlwaine reported at an international investigative dermatology meeting.

"Despite the growing knowledge of the danger of sun exposure and UV tanning, our results suggest that a large proportion of the population still believes tanning is desirable and attractive. Until public opinion changes, it's important to provide the public with suitable ways to tan their skin without the dangers of UV exposure—such as STPs," she added at the meeting of the European Society for Dermatological Research, the Japanese Society for Investigative Dermatology, and the Society for Investigative Dermatology.

She surveyed 415 women, average age 28 years, regarding their tanning behaviors and beliefs. The women were queried in gyms, swimming pools, and university sororities and dining halls.

Forty-eight percent of respondents reported using STPs at least once in the past year. "That's a much higher percentage than in previous published studies. This suggests STP use may be increasing," according to Ms. McIlwaine, who is a medical student at Emory University in Atlanta.

Encouragingly, 35% of the STP users indicated they employed these "tan-in-a-can" products as at least a partial replacement for sunbathing, and 25% reported using STPs in lieu of tanning beds.

STPs appear to be more popular with younger women. Fifty-four percent of 18-to 25-year-olds reported using them within the past year, compared with 41% of those aged 26-40 years and 40% of respondents over the age of 40.

Only 14% of women with brown or black skin reported STP use, compared with 56% of those with very white/freckled skin and 54% with white/olive skin.

The survey results suggest that, in spite of the growing awareness of the dangers of UV tanning, core ideas regarding the desirability of the tanned look remain largely unchanged. Ninety-three percent of the survey respondents indicated they believe tanned skin is more attractive than untanned skin. Seventy-nine percent said that they feel better about themselves when they have a tan. Seventy-one percent of subjects reported sunbathing at least once during the past year, and 26% used a tanning bed.

Most STPs contain dihydroacetone, which reacts with amino acids in the stratum corneum to produce a temporary brown hue.

Respondents' top reasons for not using STPs were dislike of product color and streakiness. Thus, further technical improvements in product quality might be important in achieving greater public acceptance and more widespread use of STPs as a tool for skin cancer prevention, Ms. McIlwaine concluded.

"Tan-in-a-can" products appear to be more popular with younger women. Shane Wake

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

More young adults now say that they value the appearance of a tan than have said so in past years, and their increased use of indoor tanning reflects that attitude, according to Dr. June K. Robinson of Northwestern University, Chicago, and her associates.

Researchers surveyed 100 people who appeared to be aged 18-30 years, and were sitting or lying on a Chicago beach in July of last year, about their knowledge of, attitudes toward, and use of indoor tanning, and compared the results with telephone surveys of 1,000 Illinois residents conducted in 1988 and with 958 teenage and young adult Chicagoans in 1994.

The 38 men and 62 women in the present survey were matched for age and sex with 100 subjects in each earlier survey.

The knowledge that tanning can cause melanoma/skin cancer initially decreased from 42% in the 1988 survey to 38% in the 1994 survey but then increased to 87% in 2007, Dr. Robinson and her associates reported (Arch. Dermatol. 2008;144:484-8).

Nevertheless, they said, "in each successive interval, there was an almost equivalent increase in the perception that people looked better with a tan"—from 58% to 69% and finally to 81% in 2007.

Tanning bed use also rose from 1% in 1988 to 26% in 1994 and 27% in 2007.

In all years surveyed, respondents said that they got most of their information about the general safety of indoor tanning beds from their friends or social group (71%-75%) and half reported that they went to a tanning salon for the first time with their friends. Other sources of information included family (18%-21%) and tanning salon workers (23%-24%).

Adolescents and young adults said their most trusted source of information about indoor tanning was the family physician or dermatologist, but only 15% reported that they had ever discussed the issue with their physicians, Dr. Robinson and her associates found.

"Counseling young adult patients to cease indoor tanning represents an opportunity to prevent UV radiation exposure that may cause melanoma," they noted.

CHICAGO — The Sunbelt melanoma study did not meet its primary end point of showing a benefit of high-dose interferon in melanoma patients with a single positive sentinel lymph node, reported the principal investigator at the annual meeting of the American Society of Clinical Oncology.

In neither of two protocols comparing high-dose interferon to observation did the treatment arms show a significant benefit in either 5-year disease-free survival or overall survival among patients with a single positive node confirmed by histology or molecular studies.

Dr. Kelly McMasters, chief of the division of surgical oncology at the University of Louisville (Ky.), presented the data on behalf of his colleagues in the Sunbelt Melanoma Trial Group. The investigator-initiated trial, which involved 79 centers in the United States and Canada, registered 3,619 patients from the ages of 18 to 70 years with cutaneous melanomas with a thickness of at least 1 mm and no clinical evidence of regional nodal or distant metastases. Of these 1,781 were reported in the intention-to-treat analyses.

The patients were stratified according to Breslow thickness: 1.0-2.0 mm, 2-4 mm, and greater than 4 mm, and the presence or absence of ulceration.

The trial had two protocol arms and an unusually complex design. All patients underwent sentinel node biopsy, and those with a node that was confirmed positive on histology were eligible for protocol A, which involved completion lymph node dissection.

Patients with only one microscopically positive node were then randomized to either an observation arm (arm 1, with 112 patients) or to a treatment arm with high-dose interferon alfa-2b (Intron A) for 12 months (arm 2, 106 patients).

Patients with more than one positive lymph node or extracapsular extension were assigned to receive high-dose interferon for 12 months and were followed (arm 3, with 99 patients).

In protocol B, those patients who had histologically negative results after sentinel node biopsy subsequently had their sample tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for molecular staging to detect the presence of occult melanoma cells. Those who were RT-PCR-positive were then randomized to either observation (arm 4, with 180 patients), completion lymph node dissection (arm 5, with 192 patients), or completion lymph node dissection plus interferon (arm 6, with 184 patients). Patients who were RT-PCR-negative were assigned to observation alone (arm 7, with 908 patients).

Dr. McMasters presented intention-to-treat analyses for each protocol. In protocol A, for patients with a single histologically positive sentinel node, the 5-year disease-free survival was 70.2% for arm 1 (the observation group) and 73.2% for arm 2 (the interferon group) (log-rank P = .4589). Five-year overall survival in these patients was 75.4% among patients on observation vs. 72.9% for those on interferon (P = .9033).

There were, however, statistically significant decreases in both disease-free and overall survival for patients in protocol A with more than one positive lymph node (arm 3), compared with arms 1 and 2. The 5-year disease-free survival for patients in arm 3 was 44.5% (P less than .0001 vs. arms 1 and 2), and overall survival was 52.9% (P = .0004).

In the disease-free survival analysis in protocol B, there were similarly no significant differences among patients randomized to observation, completion lymph node dissection, or completion lymph node dissection with interferon, with rates of 83.9%, 85.2%, and 83.7%, respectively.

For the same groups in the overall survival analysis, there were no significant differences, with rates of 85.5% for the observation arm, 85.3% for the node dissection alone arm, and 86.8% for the node dissection plus IFN arm. Similarly, there were no significant differences in either disease-free survival in protocol B between patients who were node-negative or node-positive on RT-PCR, or in overall survival, which indicated that PCR testing for melanoma cells was not prognostically significant in this study, Dr. McMasters remarked.

A comparison of all the patient treatment arms in the study showed that patients who were histologically node-negative (those in arms 4, 5, 6, and 7 combined) had a better overall survival rate than those with a single positive sentinel node (patients in arms 1 and 2 combined), who in turn did better than those who had more than one positive node or extracapsular extension (those in arm 3) (P less than .0001).

In protocol A, "our results did not support the use of high-dose interferon for patients with a single microscopically positive sentinel node," Dr. McMasters said.

In protocol B, the results do not support the use of completion lymph node dissection or interferon for node-negative patients, and indicate that RT-PCR staging of sentinel lymph nodes was not predictive of worse outcome.

Dr. McMasters noted that the study was underpowered to detect small differences in disease-free survival and overall survival, "but we also did not observe significant trends, and even large sample size will not make differences appear if they don't exist."

The study was supported by a grant from Schering Oncology Biotech. Dr. McMasters and several other investigators have been on the speakers bureau.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The Sunbelt melanoma study did not meet its primary end point of showing a benefit of high-dose interferon in melanoma patients with a single positive sentinel lymph node, reported the principal investigator at the annual meeting of the American Society of Clinical Oncology.

In neither of two protocols comparing high-dose interferon to observation did the treatment arms show a significant benefit in either 5-year disease-free survival or overall survival among patients with a single positive node confirmed by histology or molecular studies.

Dr. Kelly McMasters, chief of the division of surgical oncology at the University of Louisville (Ky.), presented the data on behalf of his colleagues in the Sunbelt Melanoma Trial Group. The investigator-initiated trial, which involved 79 centers in the United States and Canada, registered 3,619 patients from the ages of 18 to 70 years with cutaneous melanomas with a thickness of at least 1 mm and no clinical evidence of regional nodal or distant metastases. Of these 1,781 were reported in the intention-to-treat analyses.

The patients were stratified according to Breslow thickness: 1.0-2.0 mm, 2-4 mm, and greater than 4 mm, and the presence or absence of ulceration.

The trial had two protocol arms and an unusually complex design. All patients underwent sentinel node biopsy, and those with a node that was confirmed positive on histology were eligible for protocol A, which involved completion lymph node dissection.

Patients with only one microscopically positive node were then randomized to either an observation arm (arm 1, with 112 patients) or to a treatment arm with high-dose interferon alfa-2b (Intron A) for 12 months (arm 2, 106 patients).

Patients with more than one positive lymph node or extracapsular extension were assigned to receive high-dose interferon for 12 months and were followed (arm 3, with 99 patients).

In protocol B, those patients who had histologically negative results after sentinel node biopsy subsequently had their sample tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for molecular staging to detect the presence of occult melanoma cells. Those who were RT-PCR-positive were then randomized to either observation (arm 4, with 180 patients), completion lymph node dissection (arm 5, with 192 patients), or completion lymph node dissection plus interferon (arm 6, with 184 patients). Patients who were RT-PCR-negative were assigned to observation alone (arm 7, with 908 patients).

Dr. McMasters presented intention-to-treat analyses for each protocol. In protocol A, for patients with a single histologically positive sentinel node, the 5-year disease-free survival was 70.2% for arm 1 (the observation group) and 73.2% for arm 2 (the interferon group) (log-rank P = .4589). Five-year overall survival in these patients was 75.4% among patients on observation vs. 72.9% for those on interferon (P = .9033).

There were, however, statistically significant decreases in both disease-free and overall survival for patients in protocol A with more than one positive lymph node (arm 3), compared with arms 1 and 2. The 5-year disease-free survival for patients in arm 3 was 44.5% (P less than .0001 vs. arms 1 and 2), and overall survival was 52.9% (P = .0004).

In the disease-free survival analysis in protocol B, there were similarly no significant differences among patients randomized to observation, completion lymph node dissection, or completion lymph node dissection with interferon, with rates of 83.9%, 85.2%, and 83.7%, respectively.

For the same groups in the overall survival analysis, there were no significant differences, with rates of 85.5% for the observation arm, 85.3% for the node dissection alone arm, and 86.8% for the node dissection plus IFN arm. Similarly, there were no significant differences in either disease-free survival in protocol B between patients who were node-negative or node-positive on RT-PCR, or in overall survival, which indicated that PCR testing for melanoma cells was not prognostically significant in this study, Dr. McMasters remarked.

A comparison of all the patient treatment arms in the study showed that patients who were histologically node-negative (those in arms 4, 5, 6, and 7 combined) had a better overall survival rate than those with a single positive sentinel node (patients in arms 1 and 2 combined), who in turn did better than those who had more than one positive node or extracapsular extension (those in arm 3) (P less than .0001).

In protocol A, "our results did not support the use of high-dose interferon for patients with a single microscopically positive sentinel node," Dr. McMasters said.

In protocol B, the results do not support the use of completion lymph node dissection or interferon for node-negative patients, and indicate that RT-PCR staging of sentinel lymph nodes was not predictive of worse outcome.

Dr. McMasters noted that the study was underpowered to detect small differences in disease-free survival and overall survival, "but we also did not observe significant trends, and even large sample size will not make differences appear if they don't exist."

The study was supported by a grant from Schering Oncology Biotech. Dr. McMasters and several other investigators have been on the speakers bureau.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — The Sunbelt melanoma study did not meet its primary end point of showing a benefit of high-dose interferon in melanoma patients with a single positive sentinel lymph node, reported the principal investigator at the annual meeting of the American Society of Clinical Oncology.

In neither of two protocols comparing high-dose interferon to observation did the treatment arms show a significant benefit in either 5-year disease-free survival or overall survival among patients with a single positive node confirmed by histology or molecular studies.

Dr. Kelly McMasters, chief of the division of surgical oncology at the University of Louisville (Ky.), presented the data on behalf of his colleagues in the Sunbelt Melanoma Trial Group. The investigator-initiated trial, which involved 79 centers in the United States and Canada, registered 3,619 patients from the ages of 18 to 70 years with cutaneous melanomas with a thickness of at least 1 mm and no clinical evidence of regional nodal or distant metastases. Of these 1,781 were reported in the intention-to-treat analyses.

The patients were stratified according to Breslow thickness: 1.0-2.0 mm, 2-4 mm, and greater than 4 mm, and the presence or absence of ulceration.

The trial had two protocol arms and an unusually complex design. All patients underwent sentinel node biopsy, and those with a node that was confirmed positive on histology were eligible for protocol A, which involved completion lymph node dissection.

Patients with only one microscopically positive node were then randomized to either an observation arm (arm 1, with 112 patients) or to a treatment arm with high-dose interferon alfa-2b (Intron A) for 12 months (arm 2, 106 patients).

Patients with more than one positive lymph node or extracapsular extension were assigned to receive high-dose interferon for 12 months and were followed (arm 3, with 99 patients).

In protocol B, those patients who had histologically negative results after sentinel node biopsy subsequently had their sample tested with reverse transcriptase-polymerase chain reaction (RT-PCR) for molecular staging to detect the presence of occult melanoma cells. Those who were RT-PCR-positive were then randomized to either observation (arm 4, with 180 patients), completion lymph node dissection (arm 5, with 192 patients), or completion lymph node dissection plus interferon (arm 6, with 184 patients). Patients who were RT-PCR-negative were assigned to observation alone (arm 7, with 908 patients).

Dr. McMasters presented intention-to-treat analyses for each protocol. In protocol A, for patients with a single histologically positive sentinel node, the 5-year disease-free survival was 70.2% for arm 1 (the observation group) and 73.2% for arm 2 (the interferon group) (log-rank P = .4589). Five-year overall survival in these patients was 75.4% among patients on observation vs. 72.9% for those on interferon (P = .9033).

There were, however, statistically significant decreases in both disease-free and overall survival for patients in protocol A with more than one positive lymph node (arm 3), compared with arms 1 and 2. The 5-year disease-free survival for patients in arm 3 was 44.5% (P less than .0001 vs. arms 1 and 2), and overall survival was 52.9% (P = .0004).

In the disease-free survival analysis in protocol B, there were similarly no significant differences among patients randomized to observation, completion lymph node dissection, or completion lymph node dissection with interferon, with rates of 83.9%, 85.2%, and 83.7%, respectively.

For the same groups in the overall survival analysis, there were no significant differences, with rates of 85.5% for the observation arm, 85.3% for the node dissection alone arm, and 86.8% for the node dissection plus IFN arm. Similarly, there were no significant differences in either disease-free survival in protocol B between patients who were node-negative or node-positive on RT-PCR, or in overall survival, which indicated that PCR testing for melanoma cells was not prognostically significant in this study, Dr. McMasters remarked.

A comparison of all the patient treatment arms in the study showed that patients who were histologically node-negative (those in arms 4, 5, 6, and 7 combined) had a better overall survival rate than those with a single positive sentinel node (patients in arms 1 and 2 combined), who in turn did better than those who had more than one positive node or extracapsular extension (those in arm 3) (P less than .0001).

In protocol A, "our results did not support the use of high-dose interferon for patients with a single microscopically positive sentinel node," Dr. McMasters said.

In protocol B, the results do not support the use of completion lymph node dissection or interferon for node-negative patients, and indicate that RT-PCR staging of sentinel lymph nodes was not predictive of worse outcome.

Dr. McMasters noted that the study was underpowered to detect small differences in disease-free survival and overall survival, "but we also did not observe significant trends, and even large sample size will not make differences appear if they don't exist."

The study was supported by a grant from Schering Oncology Biotech. Dr. McMasters and several other investigators have been on the speakers bureau.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Add tremelimumab monotherapy to the list of treatments that showed potential for improving metastatic melanoma survival but have failed thus far to live up to their promise, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In an international multicenter phase III trial comparing the investigational antibody tremelimumab with standard single-agent chemotherapy, tremelimumab did not improve overall survival versus either temozolomide (Temodar) or dacarbazine (DTC), said Dr. Antoni Ribas, a medical oncologist at the University of California at Los Angeles Medical Center.

While tremelimumab didn't surpass standard chemotherapy, patients who received it had objective responses to the agent, many of which were sustained, Dr. Ribas said, concluding that it warrants further investigation for treatment of metastatic melanoma.

Tremelimumab is a fully humanized monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It blocks negative CTLA4 signaling, and has been shown in animal models and in vitro studies to induce significant activation of T cells at concentrations of 30 mcg/mL.

In a phase I/II clinical trial in 112 patients with measurable melanoma, tremelimumab produced objective responses in 11% of patients, and ongoing durable responses of 32-64 months in 8% of patients.

The phase III study was designed to test the hypothesis that tremelimumab could improve survival in patients with surgically incurable metastatic melanoma. It was funded by Pfizer Inc., developer of tremelimumab. The investigators chose a dose of 15 mg/kg on day 1 and then every 90 days.

The primary end point was overall survival with an improvement of at least 33% over the comparator, with secondary end points including best overall response, durable response, duration of tumor response, progression-free survival 6 months after randomization, and safety.

Stages IIIc and IV melanoma patients were randomized in a 1:1:1 ratio to either tremelimumab or to single-agent chemotherapy with either 1,000 mg/m

The analysis was conducted on 324 patients who were assigned to receive tremelimumab and 319 assigned to the two chemotherapy regimens.

The trial was halted early after the second interim analysis in March 2008, when the data safety monitoring board determined that the study crossed the predetermined adjusted boundary for futility (P greater than .473), with a P value of .729.

A Kaplan-Meier estimate of overall survival among all patients in an intention-to-treat analysis showed median survival rates of 11.8 months for tremelimumab and 10.7 months for chemotherapy.

In an exploratory analysis of factors associated with overall survival, the authors found that "contrary to what had been anticipated, there is a trend toward better survival in the subset of patients with less advanced disease when treated with chemotherapy as opposed to tremelimumab," Dr. Ribas said.

In an intention-to-treat analysis of responses to therapy and 6-month progression-free survival, the complete response rate among 328 patients on tremelimumab was 1.5%, compared with 1.8% for 327 patients on chemotherapy. The partial response rates were 7.6% for patients who received the antibody and 8.3% for those on chemotherapy. The objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively.

Six-month objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively. Six-month progression-free survival was 18.6% for tremelimumab, vs. 14.1% for chemotherapy; this difference was not statistically significant.

Dr. Patrick Hwu, professor and chairman of medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, questioned whether overall survival was the best end point for the study, given that a subgroup of patients had a durable response to the anti-CTLA4 antibody.

Dr. Ribas has received honoraria, research funding, and served in an advisory role to Pfizer. Three of his coauthors are employees of the company.

CHICAGO — Add tremelimumab monotherapy to the list of treatments that showed potential for improving metastatic melanoma survival but have failed thus far to live up to their promise, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In an international multicenter phase III trial comparing the investigational antibody tremelimumab with standard single-agent chemotherapy, tremelimumab did not improve overall survival versus either temozolomide (Temodar) or dacarbazine (DTC), said Dr. Antoni Ribas, a medical oncologist at the University of California at Los Angeles Medical Center.

While tremelimumab didn't surpass standard chemotherapy, patients who received it had objective responses to the agent, many of which were sustained, Dr. Ribas said, concluding that it warrants further investigation for treatment of metastatic melanoma.

Tremelimumab is a fully humanized monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It blocks negative CTLA4 signaling, and has been shown in animal models and in vitro studies to induce significant activation of T cells at concentrations of 30 mcg/mL.

In a phase I/II clinical trial in 112 patients with measurable melanoma, tremelimumab produced objective responses in 11% of patients, and ongoing durable responses of 32-64 months in 8% of patients.

The phase III study was designed to test the hypothesis that tremelimumab could improve survival in patients with surgically incurable metastatic melanoma. It was funded by Pfizer Inc., developer of tremelimumab. The investigators chose a dose of 15 mg/kg on day 1 and then every 90 days.

The primary end point was overall survival with an improvement of at least 33% over the comparator, with secondary end points including best overall response, durable response, duration of tumor response, progression-free survival 6 months after randomization, and safety.

Stages IIIc and IV melanoma patients were randomized in a 1:1:1 ratio to either tremelimumab or to single-agent chemotherapy with either 1,000 mg/m

The analysis was conducted on 324 patients who were assigned to receive tremelimumab and 319 assigned to the two chemotherapy regimens.

The trial was halted early after the second interim analysis in March 2008, when the data safety monitoring board determined that the study crossed the predetermined adjusted boundary for futility (P greater than .473), with a P value of .729.

A Kaplan-Meier estimate of overall survival among all patients in an intention-to-treat analysis showed median survival rates of 11.8 months for tremelimumab and 10.7 months for chemotherapy.

In an exploratory analysis of factors associated with overall survival, the authors found that "contrary to what had been anticipated, there is a trend toward better survival in the subset of patients with less advanced disease when treated with chemotherapy as opposed to tremelimumab," Dr. Ribas said.

In an intention-to-treat analysis of responses to therapy and 6-month progression-free survival, the complete response rate among 328 patients on tremelimumab was 1.5%, compared with 1.8% for 327 patients on chemotherapy. The partial response rates were 7.6% for patients who received the antibody and 8.3% for those on chemotherapy. The objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively.

Six-month objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively. Six-month progression-free survival was 18.6% for tremelimumab, vs. 14.1% for chemotherapy; this difference was not statistically significant.

Dr. Patrick Hwu, professor and chairman of medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, questioned whether overall survival was the best end point for the study, given that a subgroup of patients had a durable response to the anti-CTLA4 antibody.

Dr. Ribas has received honoraria, research funding, and served in an advisory role to Pfizer. Three of his coauthors are employees of the company.

CHICAGO — Add tremelimumab monotherapy to the list of treatments that showed potential for improving metastatic melanoma survival but have failed thus far to live up to their promise, investigators reported at the annual meeting of the American Society of Clinical Oncology.

In an international multicenter phase III trial comparing the investigational antibody tremelimumab with standard single-agent chemotherapy, tremelimumab did not improve overall survival versus either temozolomide (Temodar) or dacarbazine (DTC), said Dr. Antoni Ribas, a medical oncologist at the University of California at Los Angeles Medical Center.

While tremelimumab didn't surpass standard chemotherapy, patients who received it had objective responses to the agent, many of which were sustained, Dr. Ribas said, concluding that it warrants further investigation for treatment of metastatic melanoma.

Tremelimumab is a fully humanized monoclonal antibody specific for cytotoxic T lymphocyte-associated antigen 4 (CTLA4). It blocks negative CTLA4 signaling, and has been shown in animal models and in vitro studies to induce significant activation of T cells at concentrations of 30 mcg/mL.

In a phase I/II clinical trial in 112 patients with measurable melanoma, tremelimumab produced objective responses in 11% of patients, and ongoing durable responses of 32-64 months in 8% of patients.

The phase III study was designed to test the hypothesis that tremelimumab could improve survival in patients with surgically incurable metastatic melanoma. It was funded by Pfizer Inc., developer of tremelimumab. The investigators chose a dose of 15 mg/kg on day 1 and then every 90 days.

The primary end point was overall survival with an improvement of at least 33% over the comparator, with secondary end points including best overall response, durable response, duration of tumor response, progression-free survival 6 months after randomization, and safety.

Stages IIIc and IV melanoma patients were randomized in a 1:1:1 ratio to either tremelimumab or to single-agent chemotherapy with either 1,000 mg/m

The analysis was conducted on 324 patients who were assigned to receive tremelimumab and 319 assigned to the two chemotherapy regimens.

The trial was halted early after the second interim analysis in March 2008, when the data safety monitoring board determined that the study crossed the predetermined adjusted boundary for futility (P greater than .473), with a P value of .729.

A Kaplan-Meier estimate of overall survival among all patients in an intention-to-treat analysis showed median survival rates of 11.8 months for tremelimumab and 10.7 months for chemotherapy.

In an exploratory analysis of factors associated with overall survival, the authors found that "contrary to what had been anticipated, there is a trend toward better survival in the subset of patients with less advanced disease when treated with chemotherapy as opposed to tremelimumab," Dr. Ribas said.

In an intention-to-treat analysis of responses to therapy and 6-month progression-free survival, the complete response rate among 328 patients on tremelimumab was 1.5%, compared with 1.8% for 327 patients on chemotherapy. The partial response rates were 7.6% for patients who received the antibody and 8.3% for those on chemotherapy. The objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively.

Six-month objective response rates (complete and partial responses combined) were 9.1% and 10.1%, respectively. Six-month progression-free survival was 18.6% for tremelimumab, vs. 14.1% for chemotherapy; this difference was not statistically significant.

Dr. Patrick Hwu, professor and chairman of medical oncology at the University of Texas M.D. Anderson Cancer Center, Houston, questioned whether overall survival was the best end point for the study, given that a subgroup of patients had a durable response to the anti-CTLA4 antibody.

Dr. Ribas has received honoraria, research funding, and served in an advisory role to Pfizer. Three of his coauthors are employees of the company.

WILLIAMSBURG, VA. — More than half of patients who undergo organ transplantation will develop a skin cancer, often within the first 5 years after surgery, according to Dr. Henry Randle.

Most of the cancers associated with transplant surgery are squamous cell carcinomas (SCC), which tend to appear as multiple lesions that grow rapidly and exhibit a high rate of recurrence, said Dr. Randle of the Mayo Clinic, Jacksonville, Fla.

"These tumors are very aggressive and 5%-8% more likely to metastasize. They require aggressive treatment and frequent follow-up—like every 1-3 months. Don't let these patients get by without seeing you every 6 months to 1 year," he said at a meeting of the American Society for Mohs Surgery.

SCCs are up to 250 times more likely to develop in transplant patients than the rest of the population, according to Dr. Randle. These patients also have a 10-fold increased risk of basal cell carcinoma (BCC), a 3- to 5-fold increased risk of malignant melanoma, and up to an 85-fold increased risk of Kaposi sarcoma.

"It is now recognized that skin cancer constitutes 37%-50% of all de novo neoplasms in transplant patients. The typical patient has multiple actinic keratoses and warts, a reversal of the basal cell:squamous cell carcinoma ratio, and aggressive squamous cell carcinomas that may metastasize and cause death within months to years after the transplant."

He cited three severity groups:

▸ Isolated carcinogenesis. Patients have a few lesions scattered about, which can be treated with basic therapies.

▸ Moderate carcinogenesis. Patients have up to 10 skin cancers per year. They need more aggressive treatment (usually Mohs surgery), and more frequent follow-up.

▸ Catastrophic carcinogenesis. These patients can get more than 100 SCCs each year and are likely to die from the tumors. They require frequent visits and very aggressive treatment, perhaps with "megasessions," in which several lesions are removed with Mohs surgery in one treatment. This can be problematic as it usually requires general anesthesia and the sessions can be quite long, Dr. Randle said.

Mohs is not the only treatment that can benefit transplant patients, however. "We need to use all our options to treat them. That includes excisional surgery, Mohs, topical anticancer creams, and chemotherapy and radiation in selected patients," he said.

For superficial, low-risk SCC lesions, aggressive electrodesiccation and curettage or laser surgery should suffice. For large lesions, wide excision including the subcutaneous fat is necessary.

For high-risk, rapidly growing, or recurrent SCCs, Mohs is probably the choice. However, because these lesions are more prone to metastasize, a sentinel node biopsy should be considered, Dr. Randle said.

SCC lesions with in-transit metastases will require a wide excision plus radiation, "and very close follow-up, because this treatment will probably fail," Dr. Randle said.

Transplant patients with skin cancers will do better if they can reduce or eliminate their immunosuppressive medications, "but the transplant surgeons don't like that suggestion, of course. You need to walk a tightrope between rejection and skin cancer, and it's not easy," he said.

WILLIAMSBURG, VA. — More than half of patients who undergo organ transplantation will develop a skin cancer, often within the first 5 years after surgery, according to Dr. Henry Randle.

Most of the cancers associated with transplant surgery are squamous cell carcinomas (SCC), which tend to appear as multiple lesions that grow rapidly and exhibit a high rate of recurrence, said Dr. Randle of the Mayo Clinic, Jacksonville, Fla.

"These tumors are very aggressive and 5%-8% more likely to metastasize. They require aggressive treatment and frequent follow-up—like every 1-3 months. Don't let these patients get by without seeing you every 6 months to 1 year," he said at a meeting of the American Society for Mohs Surgery.

SCCs are up to 250 times more likely to develop in transplant patients than the rest of the population, according to Dr. Randle. These patients also have a 10-fold increased risk of basal cell carcinoma (BCC), a 3- to 5-fold increased risk of malignant melanoma, and up to an 85-fold increased risk of Kaposi sarcoma.

"It is now recognized that skin cancer constitutes 37%-50% of all de novo neoplasms in transplant patients. The typical patient has multiple actinic keratoses and warts, a reversal of the basal cell:squamous cell carcinoma ratio, and aggressive squamous cell carcinomas that may metastasize and cause death within months to years after the transplant."

He cited three severity groups:

▸ Isolated carcinogenesis. Patients have a few lesions scattered about, which can be treated with basic therapies.

▸ Moderate carcinogenesis. Patients have up to 10 skin cancers per year. They need more aggressive treatment (usually Mohs surgery), and more frequent follow-up.

▸ Catastrophic carcinogenesis. These patients can get more than 100 SCCs each year and are likely to die from the tumors. They require frequent visits and very aggressive treatment, perhaps with "megasessions," in which several lesions are removed with Mohs surgery in one treatment. This can be problematic as it usually requires general anesthesia and the sessions can be quite long, Dr. Randle said.

Mohs is not the only treatment that can benefit transplant patients, however. "We need to use all our options to treat them. That includes excisional surgery, Mohs, topical anticancer creams, and chemotherapy and radiation in selected patients," he said.

For superficial, low-risk SCC lesions, aggressive electrodesiccation and curettage or laser surgery should suffice. For large lesions, wide excision including the subcutaneous fat is necessary.

For high-risk, rapidly growing, or recurrent SCCs, Mohs is probably the choice. However, because these lesions are more prone to metastasize, a sentinel node biopsy should be considered, Dr. Randle said.

SCC lesions with in-transit metastases will require a wide excision plus radiation, "and very close follow-up, because this treatment will probably fail," Dr. Randle said.

Transplant patients with skin cancers will do better if they can reduce or eliminate their immunosuppressive medications, "but the transplant surgeons don't like that suggestion, of course. You need to walk a tightrope between rejection and skin cancer, and it's not easy," he said.

WILLIAMSBURG, VA. — More than half of patients who undergo organ transplantation will develop a skin cancer, often within the first 5 years after surgery, according to Dr. Henry Randle.

Most of the cancers associated with transplant surgery are squamous cell carcinomas (SCC), which tend to appear as multiple lesions that grow rapidly and exhibit a high rate of recurrence, said Dr. Randle of the Mayo Clinic, Jacksonville, Fla.

"These tumors are very aggressive and 5%-8% more likely to metastasize. They require aggressive treatment and frequent follow-up—like every 1-3 months. Don't let these patients get by without seeing you every 6 months to 1 year," he said at a meeting of the American Society for Mohs Surgery.

SCCs are up to 250 times more likely to develop in transplant patients than the rest of the population, according to Dr. Randle. These patients also have a 10-fold increased risk of basal cell carcinoma (BCC), a 3- to 5-fold increased risk of malignant melanoma, and up to an 85-fold increased risk of Kaposi sarcoma.

"It is now recognized that skin cancer constitutes 37%-50% of all de novo neoplasms in transplant patients. The typical patient has multiple actinic keratoses and warts, a reversal of the basal cell:squamous cell carcinoma ratio, and aggressive squamous cell carcinomas that may metastasize and cause death within months to years after the transplant."

He cited three severity groups:

▸ Isolated carcinogenesis. Patients have a few lesions scattered about, which can be treated with basic therapies.

▸ Moderate carcinogenesis. Patients have up to 10 skin cancers per year. They need more aggressive treatment (usually Mohs surgery), and more frequent follow-up.

▸ Catastrophic carcinogenesis. These patients can get more than 100 SCCs each year and are likely to die from the tumors. They require frequent visits and very aggressive treatment, perhaps with "megasessions," in which several lesions are removed with Mohs surgery in one treatment. This can be problematic as it usually requires general anesthesia and the sessions can be quite long, Dr. Randle said.

Mohs is not the only treatment that can benefit transplant patients, however. "We need to use all our options to treat them. That includes excisional surgery, Mohs, topical anticancer creams, and chemotherapy and radiation in selected patients," he said.

For superficial, low-risk SCC lesions, aggressive electrodesiccation and curettage or laser surgery should suffice. For large lesions, wide excision including the subcutaneous fat is necessary.

For high-risk, rapidly growing, or recurrent SCCs, Mohs is probably the choice. However, because these lesions are more prone to metastasize, a sentinel node biopsy should be considered, Dr. Randle said.

SCC lesions with in-transit metastases will require a wide excision plus radiation, "and very close follow-up, because this treatment will probably fail," Dr. Randle said.

Transplant patients with skin cancers will do better if they can reduce or eliminate their immunosuppressive medications, "but the transplant surgeons don't like that suggestion, of course. You need to walk a tightrope between rejection and skin cancer, and it's not easy," he said.