Alopecia With Endocrine Therapies in Patients With Cancer.


Abstract

Background. Whereas the frequency of alopecia to cytotoxic chemotherapies has been well described, the incidence of alopecia during endocrine therapies (i.e., anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents are widely used in the treatment and prevention of many solid tumors, principally those of the breast and prostate. Adherence to these therapies is suboptimal, in part because of toxicities. We performed a systematic analysis of the literature to ascertain the incidence and risk for alopecia in patients receiving endocrine therapies.

Methods. An independent search of citations was conducted using the PubMed database for all literature as of February 2013. Phase II–III studies using the terms “tamoxifen,” “toremifene,” “raloxifene,” “anastrozole,” “letrozole,” “exemestane,” “fulvestrant,” “leuprolide,” “flutamide,” “bicalutamide,” “nilutamide,” “fluoxymesterone,” “estradiol,” “octreotide,” “megestrol,” “medroxyprogesterone acetate,” “enzalutamide,” and “abiraterone” were searched.

Results. Data from 19,430 patients in 35 clinical trials were available for analysis. Of these, 13,415 patients had received endocrine treatments and 6,015 patients served as controls. The incidence of all-grade alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence interval: 3.3%–5.9%). The highest incidence of all-grade alopecia was observed in patients treated with tamoxifen in a phase II trial (25.4%); similarly, the overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen (6.4%). The overall relative risk of alopecia in comparison with placebo was 12.88 (p < .001), with selective estrogen receptor modulators having the highest risk.

Conclusion. Alopecia is a common yet underreported adverse event of endocrine-based cancer therapies. Their long-term use heightens the importance of this condition on patients’ quality of life. These findings are critical for pretherapy counseling, the identification of risk factors, and the development of interventions that could enhance adherence and mitigate this psychosocially difficult event.

 

Source: The Oncologist.

 

 

Baldness cure a ‘step closer’


Scientists say they have moved a step closer to banishing bald spots and reversing receding hairlines after human hair was grown in the laboratory.

Bald man combing scalp

A joint UK and US team was able to create new hairs from tissue samples.

Far more research is needed, but the group said its technique had the “potential to transform” the treatment of hair loss.

The study results were published in the journal Proceedings of the National Academy of Sciences.

There are baldness therapies including drugs to slow the loss of hairs, and transplants, which move hair from the back of the head to cover bald spots.

“Yeah I think it [baldness] will eventually be treatable, absolutely.”

Prof Colin Jahoda, Durham University

The scientists at the University of Durham, in the UK, and Columbia University Medical Centre, in the US, were trying to actually grow new hairs.

Their plan was to start with material taken from the base of a hair and use it to grow many new hairs.

Tricky feat

But human hair has been tricky to grow despite successes in animal studies.

Whenever human tissue was taken from the dermal papillae, the cells which form the base of each hair follicle, the cells would transform into skin instead of growing new hairs.

However, the group found that by clumping the cells together in “3D spheroids” they would keep their hairy identity.

Tissue was taken from seven people and grown in 3D spheroids. These were then transplanted into human skin which had been grafted on to the backs of mice.

Hair follicle
Cells were taken from the base of a follicle and used to grow new hairs

After six weeks, new hair follicles formed in five out of the seven cases and some new tiny hairs began to form.

Prof Colin Jahoda, from Durham University, told the BBC a cure for baldness was possible but it was too soon for men to be hanging up the toupee.

“It’s closer, but it’s still some way away because in terms of what people want cosmetically they’re looking for re-growth of hair that’s the same shape, the same size, as long as before, the same angle. Some of these are almost engineering solutions.

“Yeah I think it [baldness] will eventually be treatable, absolutely.”

He added: “It’s hard to say exactly how long that would take, but the fact that we’ve done it now should reawaken interest.”

Any future therapy would involve transplanting cells which have been grown in the laboratory so safety is a concern.

There would be a risk of infection and the cells could become abnormal, or even cancerous, while being grown.

Baldness cures may not be the first application of the research. Prof Jahoda believes the findings will be used to improve the quality of skin grafts used after severe burns.

Prof Angela Christiano, from Columbia University, said: “This approach has the potential to transform the medical treatment of hair loss.

“Current hair-loss medications tend to slow the loss of hair follicles or potentially stimulate the growth of existing hairs, but they do not create new hair follicles.

“Our method, in contrast, has the potential to actually grow new follicles using a patient’s own cells.”

A Possible Cure for Baldness, in 3D.


 
Set the ball rolling. Human skin cells grown on a flat culture remain dispersed and unable to induce the formation of hair follicles (left). But in a 3D culture, the cells form spheres that can coax new hair follicle growth (right).

Christiano lab, Columbia University

Set the ball rolling. Human skin cells grown on a flat culture remain dispersed and unable to induce the formation of hair follicles (left). But in a 3D culture, the cells form spheres that can coax new hair follicle growth (right).

Scientists have successfully grown new hair follicles from the skin cells of balding men. While the research team hasn’t yet shown whether the structures, which produce strands of hair on our bodies, are fully functional and usable for transplants onto a scalp, experts say the discovery is a significant step toward finding new treatments for hair loss.

“Their work is very elegant and extremely rigorous,” says Radhika Atit, a skin biologist at Case Western Reserve University in Cleveland, Ohio, who was not involved in the new study. “This is a big technical advance.”

Balding occurs when hair follicles stop producing new strands of hair in any area of the body. Now, taking drugs that prevent or slow the hair loss or transplanting hair follicles from one area of the body to another are the only viable treatments. Producing new hair follicles in the lab has not been an option—at least for human patients. In mice, researchers have shown that if they isolate dermal papilla cells, which surround hair follicles in the skin, grow them in petri dishes to produce new cells, and then put the cells back in the mouse, new hair follicles will develop. But when dermal papilla cells from humans are put into dishes in the lab, they lose their ability to induce the formation of new follicles.

Angela Christiano, a skin researcher at Columbia University who has discovered genes related to hair loss, recently brainstormed potential solutions to the problem with her colleagues. They noticed that while the dermal papilla cells from mice naturally formed large clumps in culture, the human cells didn’t. “We began thinking that maybe if we could get the human cells to aggregate like the mouse cells, that might be a step toward getting them to form new follicles,” Christiano says.

Her team decided to try a cell-growing approach, called 3D cultures, that’s been successful for other types of cells that need to form complex structures as they grow. The researchers collected dermal papilla cells from seven volunteers who had been diagnosed with male-pattern baldness. Rather than stick the isolated cells on a flat culture dish, they mixed the cells with liquid, then let the mixture hang in tiny droplets from a plastic lid, like condensation on the roof of a container. Because the cells inside the droplets are free-floating, the technique allows them to contact each other in every direction, as they would in the human body, rather than only touch side to side as they do in a flat dish. In the droplets, the cells behaved differently; as they divided to form new cells, they clumped into what the researchers call “spheroids”—balls of about 3000 cells.

To test whether the new spheroids were a better mimic for functional dermal papilla cells than those that had been grown in typical dishes, Christiano and her team determined what genes were turned on and off in different sets of dermal papilla cells. In cells grown on flat culture dishes, the expression of thousands of genes didn’t match up with their normal patterns, explaining why the cells from those dishes had been unable to generate new hair follicles. But in the 3D cultures, 22% of those genes had been restored to their correct on or off state.

The researchers then took 10 to 15 of the spheroids that had formed from each donor and sandwiched them between two layers of human skin that were grafted onto mice. Six weeks later,spheroids from five of the seven donors had coaxed the skin cells around them to start rearranging, forming the telltale shape of a hair follicle, the team reports online today in the Proceedings of the National Academy of Sciences. In two cases, hairs were even seen beginning to extend from the follicles, though the researchers didn’t continue the initial experiment for long enough to test whether the hairs were fully normal in terms of their ability to regrow.

Using one’s own cells to generate new follicles is useful because hair color and thickness will match perfectly with the rest of someone’s head of hair, Christiano notes. And with the new tissue culture technique, clinicians would be able to take just a few dermal papilla cells from a balding patient and expand the number of hair follicles available for transplant, rather than only be able to move follicles around. “Using this technique could change the number of people who would be eligible for hair transplants,” Christiano says.

The success of the approach is exciting, but the real breakthrough for other researchers in the field is the new data on gene expression in dermal papilla cells, says George Cotsarelis, a dermatologist at the University of Pennsylvania. The full readout of what genes are on and off in dermal papilla cells has never been collected before, so researchers now have a new list of thousands of genes to study further that may play key roles in hair follicle development. “It could have implications for not just hair, but treating wounds and scarring,” he says.

The spheroids capable of producing hair follicles could also be used as a new way to test drugs for their ability to restore follicle function, Atit says. “This is a better model system to use for drug testing than a two-dimensional plate.”

Factors Influencing the Effectiveness of Scalp Cooling in the Prevention of Chemotherapy-Induced Alopecia.


Abstract

Introduction. The success of scalp cooling in preventing or reducing chemotherapy-induced alopecia (CIA) is highly variable between patients and chemotherapy regimens. The outcome of hair preservation is often unpredictable and depends on various factors.

Methods. We performed a structured search of literature published from 1970 to February 2012 for articles that reported on factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer.

Results. The literature search identified 192 reports, of which 32 studies were considered relevant. Randomized studies on scalp cooling are scarce and there is little information on the determinants of the result. The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses. Temperature seems to be an important determinant. Various studies suggest that a subcutaneous scalp temperature less than 22°C is required for hair preservation.

Conclusions. The effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and probably by the degree and duration of cooling.