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Just In... Meeting News
Key news updates from recent oncology and hematology meetings.

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Sunday, May 03, 2015

 

BY MARK FUERST

 

SAN FRANCISCO--Hispanic and Asian women have an increasing risk of developing non-melanoma skin cancer, according to a study presented here at the American Academy of Dermatology Annual Meeting.

 

“Previous perception has been that the skin cancer risk in Hispanics and Asians is lower than that of Caucasians, but despite their historically lower rates, in recent years the incidence of skin cancer in these groups has been increasing in the United States,” said Arisa Ortiz, MD, Assistant Clinical Professor of Dermatology and Director of  Laser & Cosmetic Dermatology at the University of California, San Diego.

 

“Ethnic populations are not immune to skin cancer. We need to properly educate ethnic groups that skin cancer is not unique to Caucasians. In particular, clinicians need to target Hispanic and Asian women, who have an increased risk of developing skin cancer.”

 

Non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) is the most common type of malignancy in the United States, with more than 3.5 million non-melanoma skin cancers diagnosed each year. The incidence is rising at about 2.6 percent per year, and one in five Americans will be diagnosed in their lifetime.

 

“Non-melanoma skin cancers are more prevalent among Caucasians and have been well-studied in this group,” Ortiz said. “Most risk factors, characteristics, and recommendations for skin cancer prevention are based on studies of Caucasian patients. There are limited data on skin cancer in other ethnicities.”

 

Hispanics and Asians are the fastest-growing minorities in the United States and are projected to make up an even larger proportion of the population in the future, she noted. “It is important to evaluate the risk factors and clinical features of non-melanoma skin cancers in these ethic groups.”

 

She and her colleagues—first author Tiffany Loh, Alina Goldenberg, and Shang I. Brian Jiang--compared the incidence of non-melanoma skin cancers among Hispanic, Asian, and Caucasian patients presenting at the UCSD Mohs and Micrographic Surgery Unit between 2007 and 2012, comparing the risk factors and clinical characteristics of the lesions via a five-year retrospective chart review.

 

Electronic medical records contain documentation of patients’ racial self-identification, and only patients who self-identified as Caucasian, Hispanic, or Asian were included. The records were reviewed for patient age, sex, lesion location, cancer subtype, pre- and post-operation size, and number of Mohs stages required for excision.

 

The researchers found more than 4,029 cases of non-melanoma skin cancers, the vast majority (96%) of which were in Caucasians. Hispanic patients were significantly younger (age 62) than Caucasians (age 67) and Asians (age 70).

 

“The majority of non-melanoma skin cancers in Caucasians occurred in men—64 percent male and 36 percent female,” Ortiz reported. “This is the reverse gender ratio in Hispanics, which was about 34 percent male and 66 percent female, and Asians, which was about 39 percent male and 61 percent female.”

 

Significantly more non-melanoma skin cancers occur in the “central face” area in Hispanics, she noted. Race was not a significant predictor for developing a specific non-melanoma skin cancer type, either basal cell carcinoma or squamous cell carcinoma.

 

“Surprisingly, we found an increased risk of non-melanoma skin cancer in Asian and Hispanic women. In Caucasians, it is more common for men to develop this disease,” said Ortiz, adding that the reason for the gender and cultural differences will require more research.

 

Asian cultures traditionally have favored fair skin as a beauty standard, she noted, but these attitudes may have shifted in second- and third-generation families that have adopted the U.S. preference for tanning. “In Asians from Asia, fair skin is thought to be attractive. When Asians migrate to the U.S., tan skin is thought to be more beautiful.”

 

The incidence of non-melanoma skin cancer in both Hispanic and Asian patients may be impacted by indoor tanning and excessive sun exposure, Ortiz continued. Members of these populations may not have access to sun protection information, or they may believe that their darker skin tone provides them with sufficient protection. It is important, however, for Hispanic and Asian individuals to take the same skin cancer prevention measures as Caucasians.

 

The study does have limitations in that it is a single-institution study with a small sample size and geographical location, and only patients with indications for Mohs and micrographic surgery were included.

 

In conclusion, Ortiz said: “The rise of non-melanoma skin cancers in Hispanics and Asians, especially among women, is concerning given that they are the fastest growing ethnic populations in the United States. It is important that proper counseling for photoprotection be stressed to those populations to prevent any further increase.

 

Future large, multi-center studies focusing on non-melanoma skin cancer features and risk factors among minorities are necessary to further elucidate our findings.”

 

‘Skin Cancer in Skin of Color’

In a separate presentation titled “Why Skin Cancer is Important in Skin of Color,” Diane Jackson-Richards, MD, Director of the Multicultural Dermatology Center at Henry Ford Hospital in Detroit, noted that there is a need for clinics that specialize in treating skin of color. “By 2050, almost 50 percent of the U.S. population will be comprised of people with skin of color, according to the U.S. Census Bureau. Many common skin disorders present differently in skin of color, and skin of color responds differently to treatment. There is a higher frequency of some dermatologic disorders in certain ethnic groups.”

 

She noted that a recent online survey sent to dermatology chief residents and program directors asked about faculty or didactic lectures focusing on skin of color. The results showed that only 14.5 percent of programs have an expert in skin of color, less than one-quarter have experts that lecture on skin of color, and only slightly more than half have didactic lectures focusing on skin of color.

 

“Although skin cancer is much less prevalent in people of color, it is often associated with increased morbidity and mortality due to presenting at a more advanced stage. Increased education and awareness is needed.”

 

Non-melanoma skin cancer and melanoma account for 40 percent of neoplasms in Caucasians and, by contrast, in five percent of Hispanics, four percent of Asians, and two percent of Blacks. But there are racial and ethnic variations in the incidence and survival rates for cutaneous melanoma in the US.

 

The melanoma five-year survival rate among Caucasians is 92 percent compared with 86 percent among Hispanics and 78 percent among Blacks.

 

What will improve the outcome of skin cancer in patients with skin of color? Jackson-Richard asked. “Improving outcomes through early detection, improving patient awareness of their skin cancer risk, and education on appropriate sun protection.”

 

For early detection, clinicians need to “educate ourselves as well as those we are training to know the subtle differences in the presentation of skin cancer in various ethnic groups,” she said.

 

Surveys

Adoption of Western culture by Asian Americans appears to have had an effect on skin cancer rates.  An online and paper survey given to Asian Americans in northern California found that 60 percent of second-generation Westernized Asian Americans reported deliberate sunbathing compared with 47 percent of first-generation Asian Americans. The rate was only 34 percent of those raised mainly in Asia.

 

A recent survey of nearly 800 Hispanic adults examined the psychosocial correlates of sun protection behaviors. The participants resided in Arizona, California, Florida, New Mexico, or Texas and had no prior history of skin cancer. The survey included questions about suntan benefits and skin color preference, sun protection benefits and barriers, and sun protection behaviors and the perceived risk of skin cancer.  

 

About three-quarters of the respondents said they were happy with their skin color; only 11 percent said they wanted darker skin. One-quarter felt their skin color protected them, and two-thirds disagreed with the feeling that there is nothing that can be done to lower the risk of skin cancer, she reported.

 

These results are similar to a study of Caucasians that found that three-quarters reported that the benefit of using sunscreen was to prevent sunburn, she continued. One-third of the respondents did not have some type of sun protection as part of their daily routine. Barriers to sunscreen use included the perceived unpleasant feeling, the cost, not knowing what to use, and the feeling that it interfered with work or leisure, she said.

 

The lack of sun-protection behaviors among African Americans may also be a problem. A study of more than 2000 African American adults in California assessed three types of sun protection behaviors: use of sunscreen, sunglasses, and broad-brimmed hats. Respondents rated their skin type similar to a Fitzpatrick rating.

 

The results showed that about two-thirds of respondent never used sunscreen and about one-third engaged in at least one sun-protective behavior. The odds of sunscreen use increased with income and education, and women were three to six times more likely to use sunscreen than men were.

 

There are also health disparities among different ethnic and racial middle and high school students in sun exposure beliefs and knowledge. A survey with a pre- and post-test given to approximately 800 adolescents in grades 6 to 12 found that about two-thirds felt that tans were “more attractive.”

 

Caucasians had highest pre-test scores, Asians the second highest, and Blacks the lowest scores. The survey also showed that parents of darker-skinned children did not encourage sun protection.

 

Advertising

Jackson-Richards also provided information on how sunscreens are advertised. An assessment of 24 magazines for sun care products advertised from May thru September 1997 to 2002 found that these products were advertised primarily in women’s magazines. Advertising in men’s, recreation, and parenting magazines were far fewer, she said.

 

The availability of sunscreen in Hispanic neighborhoods may also be an issue. A study of 65 Spanish-speaking adults participating in community-based focus groups asked the participants about their perceived risk of skin cancer and use of sunscreens. The researchers canvassed three communities:  one primarily Hispanic, one primarily Caucasian, and one with an equal number of Caucasians and Hispanics. More than 100 merchants, including markets, pharmacies, and convenience stores, were assessed for sunscreen availability.

 

Only nine of the 65 participants (14%) considered themselves to be at risk for skin cancer. None had been taught skin self-exams. “Most did not use sunscreen because it was they said it was ‘too costly,’ ‘don’t need to,’ or ‘my skin has adapted to the sun,’” Jackson-Richards said.

 

Stores carrying sunscreen were twice as common in Caucasian neighborhoods as compared with the Hispanic ones, and Hispanic neighborhoods had fewer sunscreens to choose from.

 

Specifically Ask about Sunscreen Use

Clinicians can improve early detection of skin cancer by asking their patients specific questions about sunscreen use: “Is it in a makeup or only applied to the face? Is it only worn on vacation or for all sun-exposed activities? What is your occupation? How often do you re-apply sunscreen? What SPF is your sunscreen?”

 

Jackson-Richards said that to improve awareness, she suggests instructing patients about the advantages of self-exams. A study in Chicago that included various ethnic groups instructed patients on how to identify abnormal moles. More than three-quarters of the nearly 100 participants returned for follow-up three months later with improved knowledge of skin cancer and self-skin checks.

 

INCIDENCE

 

“Most risk factors, characteristics, and recommendations for skin cancer prevention are based on studies of Caucasian patients. There are limited data on skin cancer in other ethnicities.”

 

“The reason(s) for the gender and cultural differences will require more research.”

 

“It is important that proper counseling for photoprotection be stressed to those populations to prevent any further increase.”

 

A study in Chicago that included various ethnic groups instructed patients on how to identify abnormal moles. More than three-quarters of the nearly 100 participants returned for follow-up three months later with improved knowledge of skin cancer and self-skin checks.


Sunday, May 03, 2015

 

BY MARK FUERST

 

SAN FRANCISCO--Mortality from skin cancer increased among patients undergoing organ transplantation--in particular, for Caucasian men older than age 50, according to a U.S. population-based study presented here at the American Academy of Dermatology Annual Meeting here.

 

“The skin cancer rate is increased in transplant recipients, especially in white men over age 50,” said Sarah Tuttleton Arron, MD, PhD, Assistant Professor of Dermatology in Residence and Associate Director of the University of California, San Francisco Dermatologic Surgery and Laser Surgery. “Oncologists need to have a high index of suspicion that these patients will have a poor outcome after transplantation and treat them accordingly.”

 

There is limited populationbased data on skin cancer mortality after organ transplantation, she noted. “Our objective was to determine the U.S. incidence of skin cancer mortality after transplantation using the Organ Procurement and Transplant Network database, which captures all transplants, including cause of death.”

 

Arron, who is also Chief of Mohs Micrographic Surgery of San Francisco VA Medical Center and Director of both the High Risk Skin Cancer Program and the Dermatology Clinical Research Unit, explained that she and her colleagues researchers set out to identify the U.S. incidence density rate of skin cancer death after organ transplantation, the risk factors for skin cancer death after organ transplantation, and specific highrisk subgroups for skin cancer death after organ transplantation.

 

Study Methods

Using the database, the team identified approximately 531,000 transplants between 1987 and 2013. There were nearly 1,000 deaths due to skin cancer, for an incidence rate of 3.3 per 100 personyears and a cumulative incidence of one percent at 20 years.

 

The researchers constructed a regression model for skin cancer death on significant covariates, including male sex, age, thoracic transplant, white race, and year of transplant.

 

“We used classification and regression tree analysis to identify specific highrisk groups--notably white men over 50,” Arron said. The thoracic incidence density ratio of 18.5 per 100 personyears had a reversed hazard ratio of 5.51. The abdominal incidence density ratio of 6.5 per 100 personyears had a reversed hazard ratio of 2.09.

 

“These data demonstrate a low rate of skin cancer deaths, but identify the population at high risk,” Arron said. “The reported incidence is expected to be an underestimate due to misclassification of cause of death, particularly from cutaneous squamous cell carcinoma.

 

An ongoing Transplant Skin Cancer Network incidence study will capture additional data on skin cancer incidence and mortality after transplant, she said.

 

“Oncologists need to partner with dermatologists on the transplant team as we learn the dermatologic effects of novel cancer therapies and which drugs are safe in transplant patients,” Arron added.

 

Melanoma in Transplantation

Early-stage melanoma patients also show significantly worse outcomes after transplantation, according to a separate report by Alvin H. Chong, MBBS, MMed, Senior Lecturer in Dermatology at the University of Melbourne in Australia.

 

Chong gave an update on melanomas in transplant recipients, discussing melanoma in transplant recipients in post-transplant melanomas, pre-transplant melanomas, and melanomas from donor organs.

 

“Melanomas are the third most common malignancy in Australian renal transplant patients, and skin cancer deaths account for 37 percent of all cancer deaths,” he said.

In a study of approximately 7,500 renal transplant patients in Australia, 11 percent of all deaths were due to skin cancer. Melanoma accounted for 7.8 percent of all cancer deaths in these renal transplant recipients.

 

SCOPE Centers

Prognosis of de novo melanomas post-transplantation is poor in Europe as well, Chong noted: A voluntary study in 53 Skin Care for Organ Transplant Patients (SCOPE) centers in Europe compared survival rates among transplant recipients with melanomas with those of U.S. melanoma patients who did not have transplants and were matched for age, sex, Breslow thickness, and ulceration, using data from the American Joint Committee on Cancer (AJCC).

 

The overall prognosis of SCOPE transplant recipients with de novo melanomas was worse than the American cohort. The five-year overall survival in the SCOPE cohort was 54 percent compared with 82 percent in the AJCC cohort. Post-transplant survival outcome for less invasive melanomas in the SCOPE cohort was no different from in the AJCC cohort. However, the survival outcome was worse for SCOPE patients than the AJCC controls in those with more invasive melanomas, Chong said.

 

He cited a 2011 study of malignant melanoma in approximately 700 post-transplant recipients from Mayo Clinic, UNOS, and Israel Penn Databases. A total of 133 post-transplant melanomas with known Breslow thicknesses were found. Survival rates were stratified and compared with those in the Surveillance, Epidemiology and End Results (SEER) database for expected survival.

 

“The overall survival at three years was worse for transplant melanoma patients, compared with SEER data,” Chong said, adding that cause-specific survival was worse only for transplant melanomas that were 1.5 to 3 mm.

He noted that current data is not population-based, counts on voluntary reporting, and is non-contemporaneous.

 

“A recent systematic review of melanoma incidence and prognosis in solid organ transplant recipients concluded that population-based studies that account for melanoma stage and risk factors are needed for patients and clinicians to better understand the prognosis of pre- and post-transplant melanoma,” he said.

 

Australian Study

A recent Australian national, population-based, matched-cohort study identified approximately 8,000 melanoma patients in a transplant database. The Australian cancer database includes all Australian kidney transplant recipients with de novo invasive melanoma, who were identified by linkage.

 

Non-transplant recipients with invasive melanoma were randomly selected from cancer registry records, matched for age, sex, state of residence, and year of diagnosis--up to three per case. Similarly for transplant recipients without melanomas, who were randomly selected from database records and matched for age, sex, and state of residence--also up to three per case.

 

Data were collected by body site, histology, Breslow thickness, Clark’s level, concurrent nevus, ulceration, and overall AJCC pathologic stage. The data were analyzed to compare clinicopathologic characteristics for the probability of overall survival, including predictors of all-cause mortality.

 

The researchers found 75 kidney transplant recipients with melanomas, three-quarters of them male, about half who were diagnosed in the 1990s, with a median age at diagnosis of 55. The median time between transplantation and diagnosis was four years.

 

Three-quarters of these transplant recipients with melanomas died with a median of 6.6 years since diagnosis. In contrast, of more than 200 matched non-transplant melanoma patients, 30 percent died after a median of 27 years since diagnosis.

 

“There was no significant difference in Breslow thickness or histological subtype in transplant versus non-transplant melanoma,” Chong said. But there was a significant difference in AJCC pathologic stage and Clark’s level in transplant versus non-transplant patients. For overall survival, transplant patients with melanoma did significantly worse.”

 

In terms of melanoma-specific mortality, melanoma was reported as the cause of death in 22 of 55 (40%) of transplant melanomas and 26 of 61 (42%) in non-transplant melanomas. “Melanoma-specific mortality for transplant patients was 2.59,” he said. “Increased risk of melanoma-specific death was observed in transplant patients with Stage I, but not with Stages II, III, or IV disease,” although the study was likely underpowered to detect a mortality difference between stages.

 

“In this population-based study, non-transplant and transplant melanomas were contemporaneous, with identical methods for non-transplant and transplant. There was a long follow-up time. However, there was no centralized pathology review and no treatment data.”

 

In summary, Chong said: “Melanomas in kidney transplant recipients versus non-transplant appear to be thicker [i.e., Clark’s level] and more advanced AJCC stage at diagnosis and have lower overall survival, even with thin invasive melanomas. There is a fourfold increased risk of death, controlling for demographic and clinicopathological characteristics.”

 

Possible Mechanism of Action

The possible mechanism, he said, is inhibition of immune response to melanoma cells by iatrogenic immunosuppression from enhanced tumor growth and spread, and “biological aggressiveness.”

 

 Another likely cofactor is a greater prevalence of comorbid conditions. “Recent advances in immunotherapy target inhibitory receptor ligand pairs immune checkpoints, anti-cytotoxic T lymphocyte 4 [ipilimumab], and anti-programmed cell death-1 [nivolumab, lambrolizumab],” he noted.

 

“Circulating tumor cells are found in immunosuppressed patients, but more data is needed. Currently, there is lack of evidence regarding the benefits of reducing, altering mTOR inhibition, or discontinuing immunosuppression.”

 

There is also little evidence about the management of melanoma in transplant recipients, he continued. Expert opinion suggests the use of surgical excision with standard recommended margins and sentinel lymph node (SLN) biopsy generally at least for patients with AJCC Stage 1b disease. But SLN biopsy can be considered if melanoma has a thickness of 0.75 to 1 mm, is Clark level IV, and has increased mitoses, regression, and tumor-specific lymphocytes, he said.

 

Some studies suggest lowering immunosuppression to manage melanoma in transplant recipients. Consider using anti-angiogenic mTOR inhibition as immunosuppression, Chong said. “Sirolimus has a lower rate of malignancy compared with calcineurin inhibitors. Circulating angiogenic factors may inhibit T cell responses and promote melanoma.”  

 

Patient Education

Clinicians need to enhance patient education strategies as well, Chong said. “Educate patients to bring suspicious lesions to medical attention and to get an annual skin examination by a professional. High-risk patients should have frequent examinations. There is a low threshold for biopsy of pigmented lesions.”

 

For a patient with prior history of melanoma pre-transplant, “do not wait for in-situ melanomas,” he said. For invasive melanomas, current guidelines state to wait two to five years, depending on the melanoma and clinical situation. “There may be a role for SLN biopsy in thin primaries to determine wait time. If the lesion is more than 2 mm, consider a five-year wait.”

 

He cited a recent systematic review of donor cancer transmission in 18 kidney transplant recipients that found a prognosis of five-year survival for donor-transmitted melanoma of less than 30 percent, even after graft removal and reduction/cessation of immunosuppression. In comparison, the five-year survival for the 20 renal cancer patients in the study was 75 percent.

 

“For de novo melanomas post-transplantation, recent population-based data show that prognosis is poorer than immuno-competent patients, even for thin primary melanomas,” Chong summed up. “Management of melanomas in transplant recipients requires multidisciplinary input. The roles of SLN biopsy, lowering of immunosuppression, and mTOR inhibition is unclear. Caution is required for transplant recipients with a prior history of melanoma. Donor transplanted melanomas have a poor prognosis.”


Saturday, May 02, 2015

 

BY MARK FUERST

 

SAN FRANCISCO--Both population and genetic screening can have a positive impact on melanoma detection and treatment. That was the conclusion of those listening to a debate here at the American Academy of Dermatology Annual Meeting between Martin A. Weinstock, MD, PhD, Professor of Epidemiology and Dermatology at Brown University, and Sancy Leachman, MD, PhD, Professor and Chair of Dermatology at Oregon Health & Science University.

 

After the debate, the vast majority (90%) of the audience agreed that population screening was of primary importance, although new genetic tools show promise as well. 

 

Martin Weinstock: Population Screening

Weinstock pointed to the benefits of full-body skin exams in improving the detection of melanoma. As melanoma becomes thicker, there is a greater risk of mortality, and the relative risk goes down with clinical skin exams.

 

A study from Queensland, Australia found a 40 percent reduction in mortality with use of a clinical skin exam within three years of noticing the problem, and a 23 percent reduction in deaths from melanoma within 10 years.

 

Skin self-exams also help reduce the risks of melanoma--“Skin awareness is associated with better prognosis,” he said. Population-based case-control studies show a one-third reduction in melanoma risk with monthly exams, and a two-third reduction in fatal or advanced melanoma. “Both a clinical skin exam and self-exams reduce the risk of death from melanoma.”

 

Weinstock cited a population-based screening program at Lawrence Livermore National Laboratory that showed that after the introduction of skin screening, there was a marked increase in diagnosis of in situ melanoma among employees. At the same time, there were reductions in the thickness of melanoma lesions and a statistically significant reduction in melanoma mortality.

 

A German study also shows the advantages of population screening, Weinstock continued. At baseline, the people of Schleswig-Holstein had a moderate mortality rate from melanoma before skin screening from 1998 to 2000. Ten years later, there was a 50 percent reduction in the population-based mortality rate from melanoma.

 

The negative consequences of screening for melanoma are overdiagnosis, morbidity, and costs due to follow-up workups, treatment, and distress, he noted, defining overdiagnosis as a diagnosis made that would not have caused morbidity or death if it had not been made. “Overdiagnosis is not a medical error or malpractice, but an outcome of a health system--not individual failings.”

 

He compared melanoma screening to screening for other cancers: “The reduction of prostate cancer mortality with PSA screening is weak or nonexistent. Prostate cancer screening has a false-positive rate of 12 to 13 percent, and there is significant morbidity from evaluation and treatment of prostate cancer. With little mortality gained, recommendations are against PSA screening for prostate cancer.”

 

Breast cancer is also overdiagnosed. For example, a recent Norwegian screening program found that about 20 percent of all diagnoses of invasive breast cancer were overdiagnoses. “This likely underestimates the U.S. rates--yet still, we screen for breast cancer because it saves lives.”

 

The recent National Lung Screening Trial found that using low-dose spiral computed tomography (CT) to screen for lung cancer led to a similar number of deaths as screening with chest x-rays. “In high-risk groups, overdiagnosis is common with low-dose CT, but there is a 15 to 20 percent lower mortality with low-dose CT,” he said.

 

Population screening does lead to increased diagnoses of melanoma. In the German study, invasive melanoma diagnoses increased to 53 percent of women in Schleswig-Holstein with screening, compared with 18 percent in another city, Saarland, which had no screening. More than twice as many men in Schleswig-Holstein (26%) were diagnosed with melanoma than in Saarland (10%).

 

Randomized trials of thorough skin self-exams show that people can learn to double their skin exams over one year, and those who do the exams have about twice the number of surgeries within six months, Weinstock said.

“The screening benefit is to cut melanoma deaths, which are now at 10,000 per year in the U.S. The harms from melanoma screening are relatively minor,” he said.

 

An updated United States Preventive Services Task Force report on skin cancer screening is expected to be released in mid-2016. In 2009, the Task Force concluded there is not enough evidence to recommend for or against routine screening (total body examination by a primary care physician or patient self-examination) for early detection of skin cancers in the adult general population.

 

Sancy Leachman: Genetic Screening Impacts Melanoma

Leachman noted four types of genetic screening for melanoma:

  • Genetic predisposition testing of the blood uses individual genes versus a panel of tests to assess the risk of melanoma;
  • Genetic diagnostic testing of the tumor, a nevus, or melanoma, uses fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH), or quantitative real-time polymerase chain reaction (PCR) to assess whether the biopsy is malignant or benign;
  • Genetic prognostic testing of the primary tumor with polymerase chain reaction assesses the risk that melanoma will spread; and
  • Genetic therapeutic eligibility testing of the primary or metastasized tumor uses DNA mutations in BRAF, NRAS, and KIT to assess whether targeted therapies are an option.

 

Genetic predisposition testing informs patients at high risk before melanoma and other associated cancers develop. “If photoprotection, self-skin screening, and surveillance increase, fewer life-threatening melanomas will develop, Leachman explained. “If appropriate associated cancer screening is implemented, fewer cancers will kill. Prevention of cancer reduces morbidity secondary to surgery and therapy, and increases quality of life.”

 

Mutations in the p16 gene are the most common known cause of hereditary melanoma syndrome. Following positive p16 testing results, unaffected carriers report improvements in the thoroughness of skin self-exams, adherence to annual total-body skin exams, daily routine sun protection, use of protective clothing, and a reduced number of sunburns. Data show that about two-thirds of patients maintain these gains after two years, she said.

 

Traditional dermatopathology is highly subjective, with substantial inter-rater variability in pigmented lesions. “There is a 38 percent discordance rate among experts reviewing ‘classic’ examples of melanocytic neoplasms.”

The premise is that molecular testing is more objective and reproducible and will improve management.

 

“The ideal would be to prove that sensitivity and specificity is better than gold-standard dermatopathology with respect to outcome. The caveat is that dermatopathology is poorly validated. Favorable outcome is accurately predicted in 47 percent of cases and unfavorable outcome predicted in 73 percent of cases.”

 

Sensitivity and specificity of diagnostic tests support their benefit. For melanoma, FISH has a sensitivity range of 43 to 100 percent and a specificity range of 29 to 80 percent; CGH has a sensitivity range of 92 to 96 percent and specificity of 87 to 100 percent; and PCR has a sensitivity of 90 percent and specificity of 91 percent, she said.

 

“Genetic diagnostic testing impacts melanoma by helping to ensure that malignant lesions are appropriately excised and treated at the time of diagnosis, improving survival by decreasing recurrences. It also helps to ensure that benign lesions are not overtreated, reducing unnecessary morbidity, and reduces uncertainty and psychological or emotional distress, improving quality of life.”

 

Predictions of five-year survival rates support the benefit of gene-expression profiling (GEP), which can be used to classify stage I or II melanomas as low risk (Class 1) or high risk (Class 2) for future metastasis. She cited a recent study using GEP showing five-year disease-free survival (DFS) rates of 100 percent in a development set and 97 percent in a validation set for Class 1 patients and 38 percent in the development set and 33 percent in the validation set for Class 2 patients.

 

“GEP was a more significant and better predictor of DFS, distant metastasis-free survival, and overall survival than sentinel lymph node biopsy, and improved prognostication in combination with SLN biopsy,” she said. In SLN biopsy-negative patients with Class 2 high-risk GEP, the five-year disease-free survival rate was 35 percent, distant metastasis-free survival was 49 percent, and overall survival was 54 percent.

 

In conclusion, Leachman said: “Predisposition genetic testing to assess the risk for development of melanoma empowers high-risk patients to comply with prevention behaviors likely to reduce life-threatening disease. Diagnostic genetic testing to assess the likelihood that a lesion is malignant reduces unnecessary treatment of benign disease and improves detection and treatment of malignant disease, likely to result in improved outcome from earlier removal from a subset.

 

Prognostic genetic testing to assess the likelihood that a malignant lesion will metastasize permits increased surveillance of highest-risk individuals, likely to result in improved outcome from earlier treatment.”

 

Post-Debate Survey

The post-debate survey showed that about two-thirds of the audience still believed in the benefits of population screening, but a substantial number did switch to genetic screening--making Sancy Leachman the debate champion.


Friday, May 01, 2015

 

BY ED SUSMAN

 

VIENNA, Austria--Nipple areola skin-sparing surgical techniques may preserve sensation among women undergoing mastectomy and breast reconstruction, researchers reported here at the St. Gallen Breast Cancer Conference.

 

In a pilot study, Louis Serrurier, MD, Head of Reconstruction Services at Netcare Breast Care Centre of Excellence at Milpark Hospital in Johannesburg, South Africa, said that significantly more women reported sensation in the nipple and areola when the areola complex is preserved than among women who underwent standard reconstruction procedures.

 

“In the women with preserved areola complex the sensation in the nipple is much, much, much better than in controls,” Serrurier said. “Among the women who have the nipple areola complex preserved, about 28% of the women had an absence of sensation compared with an absence of sensation in 75% of the women who had standard surgery.”

 

He reported that in nipple reconstruction from areola-preserved skin, about 26 percent of the 18 women said nipple sensation in the left breast was excellent or good; another 46 percent of the women said there was some sensation, and 28 percent reported having no sensation.

 

Among the control group who had reconstruction done from chest wall skin, nine percent of these 11 women said they had good sensation in the nipple; 14 percent said they had some sensation; but 77 percent said they had no sensation. The right breast sensation followed the same pattern. The difference in sensation for both breasts was statistically significant, Serrurier said.

 

When the researchers tested for sensation in the left breasts among areolas reconstructed from full-thickness skin grafts with preserved skin nipple reconstruction, 24 percent of the women reported good to excellent sensation; 52 percent had some sensation; and 24 percent said they had no sensation when tested with monofilament testing devices.

 

Among the control patients, who also had areolas reconstructed with full-thickness skin grafts, 11 percent experienced good sensation; 50 percent said they experienced some sensation to the areola; and 39 percent said there was an absence of sensation. The right breast sensation results were similar. In both cases, the differences achieved statistical significance, he noted.

 

“When I perform the mastectomy and the reconstruction I really make a good effort to preserve the fourth intercostal nerve, which is the sensation to the nipple. If you preserve that nerve there is a certain amount of regeneration from it,” he said in an interview at his poster presentation.

 

“When we do a mastectomy we leave the areola behind,” he said. “There is no reason to discard it. It is not breast tissue and has no cancer risk. Using the areola we create a nipple-areola complex and then test for sensation after 18 months using monofilament.

 

“We, of course, do pathology on the specimens to make sure that we have clear margins. We remove what we need to remove to make sure there are no cancer cells in the skin we are preserving,” he explained.

 

‘Fantastic Surgery’

Commenting on the study, Lauren Cassell, MD, Chief of Breast Surgery at Lenox Hill Hospital in New York City, said:  “Nipple areola complex reconstruction is a fantastic surgery that gives women a feeling that they have their own breast. It gives women a great option for breast reconstruction. But I am still skeptical about whether they are truly getting a normal sensation.

 

“This is a prospective study, but it is a very small study,” she said, adding that it may be that the sensation felt by the women may be a response to pressure rather than true sensation.

 

For the procedure, the layer of breast tissue beneath the complex is sent to pathology while the patient is still in the operating room, Cassell explained. “If the pathologist tells you there is no cancer seen there, then you leave the nipple areolar complex. It is very rare to find any cancer there, so the risk is minimal. The nipple-sparing mastectomy is one of the major advances in breast cancer surgery.”

 

‘Wishful Thinking?’

She said that in her experience attempts to preserve nerves that allow for sensation to the nipple have not been successful, and the sensation that has been reported appears to be wishful thinking.

 

Serrurier noted that nipple areolar complex reconstruction is the final stage of breast reconstruction and plays an important role in patient satisfaction: “The surgery transforms the surgically created breast mound into a more aesthetically pleasing and natural-looking breast,” he said. “It has also been reported to make patients feel more whole and as though the breast reconstruction has been ‘completed.’”

 

While the purpose of the reconstruction is to restore the aesthetic integrity of the breast, Serrurier said, “to date, surgery cannot replace the original nipple areola complex in function. Nipple sensation is usually impaired, which disappoints many patients.”

 

He said his study describes a new technique of areola preservation at the time of skin-sparing

mastectomy, for later use of that skin to reconstruct the nipple. “To our knowledge, this technique has not been previously described in the literature. It was hypothesized that this may improve sensation of the reconstructed nipple compared with traditional methods of nipple reconstruction.”

 

The patients underwent the procedures between 2009 and 2013. The 18 patients in the new treatment group had bilateral nipple areola complex reconstruction using preserved areolar skin to reconstruct the nipple, following skin-sparing mastectomy with areolar-skin preservation. The control group of 11 patients underwent nipple areolar reconstruction using chest wall skin after mastectomy and expander-prostheses reconstruction. In both groups the areola was reconstructed with a full thickness skin graft.

 

Skin sensation was determined by testing light touch sensation using a cotton swab and pressure sensation using a Semmes-Weinstein monofilament kit, exerting between 0.07 and 300 grams of pressure. Sensation was tested in four quadrants of each nipple and each areola.

 

“We think our study confirms that the use of preserved areola skin for nipple reconstruction confers significantly better sensation in the reconstructed nipple than conventional techniques of nipple areola complex reconstruction,” Serrurier concluded.


Friday, May 01, 2015

 

BY ED SUSMAN

 

VIENNA, Austria--The latest entry into direct-acting antiviral treatment for hepatitis C virus (HCV) infection--a leading cause of liver cancer--allows patients to achieve sustained virologic responses across a broad spectrum of conditions, researchers reported here at the International Liver Congress.

 

The investigational combination, being developed by Merck, is a fixed-dose tablet containing 100 mg of the HCV NS3/4A protease inhibitor grazoprevir and 50 mg of the HCV NS5A replication complex inhibitor elbasvir that is taken once daily for 12 weeks.

 

In the pivotal C-Edge Phase III randomized, placebo-controlled trial, 299 of 316 patients—95 percent of the study population--achieved a sustained virologic response 12 weeks after the treatment ended (SVR12, considered a functional cure of the disease), reported K. Rajender Reddy, MD, Director of Hepatology at the University of Pennsylvania. The patients in the study had not received any previous treatments for Hepatitis C.

 

When the patients were stratified by HCV genotype, 144 of 157 patients (92%) who were diagnosed with Genotype 1a achieved SVR12; 129 of 131 patients or 99% who were diagnosed with Genotype 1b achieved SVR12; all 18 patients diagnosed with Genotype 4 achieved SVR12, and eight of 10 patients diagnosed with Genotype 6 achieved SVR12.

 

Reddy suggested that because of the small numbers of patients with HCV Genotype 6, further trials would be necessary to say with confidence how well the investigative combination or other treatments fared in this subtype of HCV.

 

“We think that this combination provides another excellent option for treatment of HCV infection. I think we need more options. It appears to be successful in various genotypes, and the pill burden is less than for other regimens, which typically require four to 10 pills a day--this is just one pill, once a day.”

 

When the researchers scrutinized the treatment effect by multiple subgroups--sex, age, race, cirrhosis status, and baseline HCV RNA levels--there were no statistically significant differences expected for HCV levels. All 94 patients with baseline levels of HCV of 800,000 IU/mL or less achieved SVR12 compared with 92.3 percent of the 222 patients who presented with levels higher than 800,000 IU/mL.

 

“An important aspect of this trial is that we included a placebo group in order to assess side effects of the treatment,” Reddy noted. “Patients want to know what to expect from treatment, but it is often difficult to assess that because there are also side effects that are caused by the disease.”

 

In the study design, four weeks after undergoing 12 weeks of placebo, this group of patients was switched to the active agents.

 

Side Effects

A total of 18 percent of the 316 patients on the active combination complained of headache, compared with 17 percent of the 105 patients who initially were in the placebo group; 16 percent of the treatment group and 17 percent of the placebo patients complained of fatigue; nine percent of the treatment group and eight percent of the placebo patients reported nausea; and six percent of patients from both groups reported arthralgia.

 

“This tells us that the side effect profile is quite good for this regimen,” he said in a news conference.

 

Similarly, the rate of adverse events, serious adverse events, drug-related adverse events, and discontinuations due to adverse events were similar for both patients on the active treatment and those on placebo even when stratified for those with and without cirrhosis.

 

Two patients on the active treatment died during the trial--one due to coronary disease and the other from complication for treatment of a strangulated hiatal hernia. Neither of those events was considered to be related to treatment.

 

“While cirrhosis has been traditionally considered a condition for negative response, in this trial these patients did fairly well, with 68 of the 70 patients with cirrhosis achieving an SVR12,”  Reddy reported. He explained that regimens containing ribavirin and early generations of direct acting antivirals were difficult for patients with cirrhosis to tolerate, and often cirrhotic patients would require 24 weeks of therapy in order to achieve SVR12.

 

The moderator of the news conference, Laurent Castera, MD, a hepatology specialist at Hospital Beaujon-University of Paris-VII and Vice-secretary of the study’s sponsor, the European Association for the Study of the Liver, noted that all the patients in the study had compensated or early cirrhosis.” And there is debate over where the cutoff for the definition of cirrhosis is made, the bottom line in the C-Edge study was that these patients were relatively healthy from a cirrhosis point of view, he said.

 

‘Very Exciting Combination’

“I think this combination is very exciting,” said David Bernstein, MD, Chief of the Division of Hepatology at North Shore University Hospital in Manhasset, NY. “This regimen is very well tolerated, and we are seeing excellent results. I think it will be an important addition to the market, especially for a population that we have difficulty treating now--those patients with renal disease.”

 

In one of several trials with the grazoprevir/elbasvir combination presented at the congress, the so-called C-Surfer trial examined outcomes among patients with HCV and chronic kidney disease. In that Phase II/III trial, researchers enrolled patients with advanced chronic kidney disease--that is, patients with Stage 4 or 5 disease. After 12 weeks of treatment with grazoprevir/elbasvir 115 of 116 patients diagnosed with HCV Genotype 1 disease achieved SVR12.

 

‘Unmet Need’

“There is an unmet medical need to treat chronic hepatitis C virus infection in patients with advanced chronic kidney disease,” noted Howard Monsour, Jr., MD, Chief of Hepatology at Houston Methodist Hospital. He noted that C-Surfer is the first trial to investigate an all-oral ribavirin-free treatment regimen in treatment-naïve and treatment-experienced chronic kidney disease patients.

 

The ongoing trail randomized patients to immediate treatment or delayed treatment with a placebo control arm. In addition, 11 patients received grazoprevir plus elbasvir once-daily for 12 weeks with intensive pharmacokinetic sampling.

 

About 75 percent of the patients in the study were on hemodialysis, attesting to the extent of chronic kidney disease in the study population. About 45 percent of the patients were African Americans.

 

Bernstein, in commenting on the various studies in the grazoprevir/elbasvir constellation, suggested that the combination might increase access to treatment through cost reduction: “I’m confident that approval of this combination will provide further competition that may drive costs down. Costs are already starting to come down, so I have hopes that this will further increase that downward trend once it becomes available.”