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Thursday, March 23, 2017

For many men newly diagnosed with early-stage prostate cancer, concerns about potential quality-of-life issues often guide treatment decisions. A new study led by UNC Lineberger Comprehensive Cancer Center researchers identifies distinct patterns of side effects that patients could use to guide their choices (JAMA 2017;317(11):1141-1150).

The study examines quality-of-life outcomes for the treatment choices most patients will face. Those choices include active surveillance, radical prostatectomy, external beam radiation treatment, and brachytherapy. "Patients diagnosed with early-stage prostate cancer -- and that's the vast majority of patients with this disease -- face many treatment options that are thought to be similarly efficacious," said Ronald C. Chen, MD, MPH, UNC Lineberger member and Associate Professor in the UNC School of Medicine Department of Radiation Oncology. "Therefore, the quality-of-life differences among these options become an important consideration when patients are trying to make their decisions."

The study is needed as prostate cancer treatment technologies have advanced, and as active surveillance has emerged as an important strategy for sparing low-risk prostate cancer patients unnecessary side effects. Many patients with low-risk prostate cancer on active surveillance may be able to avoid treatment for several years or altogether. ASCO has endorsed active surveillance for most men with low-risk prostate cancer.

"There has not been a large-scale comparison of the quality-of-life impact for these modern options, until now," Chen said. "Existing quality of life studies have studied older types of surgery and radiation that are no longer used, and patients need updated information regarding the impact of modern treatment options so they can make informed decisions about the choices they face today."

For the study, UNC Lineberger researchers surveyed 1,141 men who were diagnosed with early-stage prostate cancer between January 2011 and June 2013. They compared patients' self-reported quality of life related to bowel, urination, and sexual function across four strategies: active surveillance; prostatectomy; external beam radiotherapy; and brachytherapy. Almost all prostatectomy patients received robotic surgery, and almost all external beam radiotherapy patients received intensity-modulated radiation, reflecting modern treatment technologies.

Prostatectomy was linked to higher sexual dysfunction and urinary leakage than the other options. At 2 years after treatment, more than 57 percent of men who had normal sexual function prior to treatment reported poor sexual function after surgery, compared with 27 percent who reported poor sexual function after external beam radiation, 34 percent after brachytherapy, and 25 percent after active surveillance. "With modern robotic surgery, sexual dysfunction and urinary incontinence continue to be some of the side effects that surgery can cause," Chen said. "While we do see improvement over time, even at the two-year point, surgery still causes more of these issues than other treatments."

Meanwhile, other treatment choices were linked to worse scores for other side effects. External beam radiotherapy and brachytherapy caused more short-term urinary tract obstruction and irritation, while external beam radiotherapy was linked to more short-term bowel symptoms.

For the group of men who chose active surveillance, urinary issues and sexual function worsened over time. This is likely partly due to aging, and partly due to some men who experienced cancer progression that necessitated treatments that caused these side effects.

"At the 2-year time point, patients who chose radiotherapy or brachytherapy actually had quality-of-life results similar to patient who chose active surveillance, and that may be surprising to some patients," Chen said. "With advances in treatment technologies for both surgery and radiation, patients and physicians today must base their decisions on the quality-of-life results of modern treatments, not on results for outdated treatment modalities that caused much more side effects historically." Overall, Chen said the data can help patients weigh their treatment options based on their own baseline health and on their priorities.

"With all of the modern treatment options, patients should have accurate and realistic expectations about the frequency of side effects from treatment," Chen concluded\. "We found that the different treatment options have trade-offs in side effects. Each patient can look at these data to see what they care about most."​


Sunday, March 12, 2017

​​Concern about sexual activity is declining as a reason parents do not get their daughters the human papillomavirus (HPV) vaccine, according to a research study presented at the Society of Gynecologic Oncology's 2017 Annual Meeting on Women's Cancer.

Instead, according to a study presented by lead researcher Anna Beavis, MD, MPH, an SGO member and gynecologic oncologist fellow at Johns Hopkins University, parents continue to not see the vaccine as a necessity and are concerned about side effects and safety. The HPV vaccine, introduced in 2006, is used to prevent adolescents from contracting the HPV virus, which causes almost all cases of cervical cancer in women, as well as several other cancers.

"With the new nine-valent vaccine, almost 90 percent of all cervical cancer could be prevented if all adolescents were vaccinated," Beavis said. "Yet unfortunately, vaccination rates in the U.S. have lagged considerably behind those of other Westernized nations."

 The data presented compared the National Immunization Survey, or NIS-Teen, data, from 2010-2014, which reported on U.S. parents' responses to a question about why they did not vaccinate their daughters against HPV and did not intend to in the next 12 months.

From 2010-2014, the top two reasons were the concerns regarding safety and side effects and the belief the vaccine is not necessary. Yet, the third most common reason, adolescents' lack of sexual activity, dropped as a reason for parents not vaccinating. According to the data, in 2010, 18 percent of parents reported adolescents lack of sexual activity a reason, but in 2014 it dropped to 9 percent.

Prior literature has shown that physicians often delay or do not discuss HPV vaccination with parents because they feel they would also have to address sexual activity, Beavis said. Yet, the data show that parents need to understand the necessity and safety as well as the benefits of cancer prevention.

Additionally, the vaccine produces a stronger immune response in younger children, and thus only two shots instead of three are recommended if the vaccine is given to children under the age of 15. 

"Physicians should not be afraid to discuss the HPV vaccine with parents," Beavis concluded. "Our focus should be on cancer prevention."

​ 


Thursday, March 2, 2017

Women who consumed a diet as adolescents or young adults associated with chronic inflammation had a higher risk for premenopausal breast cancer compared with those whose adolescent and early adulthood diet was not associated with chronic inflammation, according to data published in Cancer Research (2017; doi: 10.1158/0008-5472.CAN-16-2273).

"A diet low in vegetables and high in sugar-sweetened and diet soft drinks, refined sugars and carbohydrates, red and processed meats, and margarine has been linked to high levels of inflammatory markers in the blood," said Karin B. Michels, ScD, PhD, Professor and Chair of the Department of Epidemiology at the UCLA Fielding School of Public Health, Los Angeles. "Because breast cancer takes many years to arise, we were curious whether such a diet during the early phases of a woman's life is a risk factor for breast cancer.

"Our results suggest that a habitual diet that promotes chronic inflammation when consumed during adolescence or early adulthood may indeed increase the risk of breast cancer in younger women before menopause," continued Michels. "During adolescence and early adulthood, when the mammary gland is rapidly developing and is therefore particularly susceptible to lifestyle factors, it is important to consume a diet rich in vegetables, fruit, whole grains, nuts, seeds, and legumes and to avoid soda consumption and a high intake of sugar, refined carbohydrates, and red and processed meats."

For this study, Michels and colleagues used data from 45,204 women enrolled in the Nurses' Health Study II who had completed a food frequency questionnaire in 1998, when they were ages 33–52, about their diet during high school. Adult diet was assessed first using a food frequency questionnaire in 1991, when participants were ages 27–44, and then every 4 years after that. Each woman's diet was given an inflammatory score using a method previously developed that links diet with inflammatory markers in the blood.

During 22 years of follow-up, 870 of the women who completed the high school food frequency questionnaire were diagnosed with premenopausal breast cancer and 490 were diagnosed with postmenopausal breast cancer.

When women were divided into five groups based on the inflammatory score of their adolescent diet, those in the highest score group had a 35 percent higher risk for premenopausal breast cancer relative to those in the lowest score group. When the same analysis was done based on early adulthood diet, those in the highest inflammatory score group had a 41 percent higher risk for premenopausal breast cancer relative to those in the lowest score group.

Diet inflammatory score was not associated with overall breast cancer incidence or postmenopausal breast cancer.

"About 12 percent of women in the United States develop breast cancer in their lifetimes," said Michels. "However, each woman's breast cancer risk is different based on numerous factors, including genetic predisposition, demographics, and lifestyle. Our study suggests that a habitual adolescent/early adulthood diet that promotes chronic inflammation may be another factor that impacts an individual woman's risk."

According to Michels, it is important to note that although this is an association study, it is not feasible to perform a causal study because that would require randomizing individuals to a particular diet for a long period of time and following them for decades. She also explained that the main limitations of the current study are that diet during adolescence was recalled by the participants at a later date and that the researchers did not have adolescent or early adulthood measurements of blood markers of inflammation in this study.​


Tuesday, February 28, 2017

For women with a rare subtype of epithelial ovarian or peritoneum cancer, known as low-grade serous carcinoma (LGSC), hormone maintenance therapy (HMT) may significantly improve survival, according to a new study from researchers at The University of Texas MD Anderson Cancer Center in Houston (J Clin Oncol 2017:  doi: 10.1200/JCO.2016.71.0632).

Should this new retrospective data be validated in a randomized study, the findings could one day represent a significant improvement to frontline standard of care.

According to the researchers, LGSC accounts for just 10 percent of serous carcinomas of the ovary/peritoneum. It is typically diagnosed in women, as early as in their 40s and 50s (however, teenagers and women in their 20s and 30s also may be diagnosed). Patients usually present with advanced disease.

"There is a true unmet need for these patients—roughly 70 percent of women with this disease will experience a recurrence of the cancer at some point," said David M. Gershenson, MD, Professor, Gynecologic Oncology and Reproductive Medicine, MD Anderson, and the study's corresponding author. "Our group published research demonstrating that hormonal therapy showed promise in the recurrent setting, with most patients responding or having stable disease. It was a natural progression over time that we began to study this up front, after women received their primary chemotherapy."

In this retrospective cohort study, researchers analyzed data from 203 women with stage II-IV LGSC treated at MD Anderson between 1981 and 2013 to evaluate the effect of HMT, compared with surveillance, after surgery, and chemotherapy. Women who received HMT (70 patients) showed an average progression-free survival (PFS) of 64.9 months compared with 26.4 months for those in the surveillance group (133 patients). Overall survival (OS) was 115.7 months following HMT versus 102.7 months for the surveillance group.

Further, among 149 women who showed no evidence of disease following completion of primary chemotherapy, HMT appears to have resulted in even greater survival: 81.1 months versus 30 months PFS; and 191.3 months versus 106.8 months OS.

"Hormonal therapy has shown promising results in reducing cancer recurrence, and there is increasing interest in integrating this approach into first-line therapy," said Gershenson. "If confirmatory research in a clinical trial setting shows hormonal maintenance therapy can prevent or delay recurrence of this cancer subtype, it would be practice-changing."

Though recruitment for this patient population is challenging given the rarity of the disease, Gershenson noted a prospective international phase III clinical trial has been designed. The study will compare chemotherapy and observation; chemotherapy and HMT; and hormonal therapy alone, which also has shown early promise in other studies.

 


Tuesday, February 28, 2017

A team of 18 researchers from the University of California San Diego School of Medicine and Moores Cancer Center have developed a new tool to analyze an often overlooked aspect of cancer genetics—an alteration that results in the loss or gain in a copy of a gene (Nature Communications 2017; doi: 10.1038/ncomms14423).

This change, known as somatic copy-number alterations, may be key to disease progression and might offer new therapeutic approaches for ovarian cancer and other malignancies.

"When most people think about cancer genetics, they think about single key mutations that foster tumor formation—very specific things like the BRCA genes," said Joe R. Delaney, PhD, a fellow in the Clinical Translation program at UC San Diego Moores Cancer Center and lead author of the paper. "These changes are often referred to as tumor drivers, but these are not the only deviations that impact cancer growth. We explored other possibilities."

More than 90 percent of genetic changes in cancer cells involve the loss or gain of a single copy of a gene, rather than a mutation. A tumor cell might have one copy or three instead of the normal two copies—one provided by each parent. This area has not been explored in depth, since experience with other diseases has taught scientists that the loss of one gene copy might not lead to disease symptoms because the second copy provided by the other parent fills in.

Delaney and team wondered if this were true if several single gene copies that cooperated for the same cellular function were lost, and what the patterns might be in different cancers. The team designed the Haploinsufficient/Triplosensitive Gene (HAPTRIG) computational tool to identify pathways significantly disrupted by the loss and gain of genes.

Ovarian cancer in particular is fraught with these alterations—with more than 60 percent of genes affected. When the team analyzed this malignancy using HAPTRIG, the pathway that stood out was autophagy—a natural process of cell death that helps maintain normal cellular health. Ovarian cancer cells use autophagy all of the time, but also lose several copies of autophagy genes resulting in a compromised capacity.

The researchers then used a combination of existing FDA-approved drugs to target autophagy and found ovarian cancer cells to be highly sensitive to these drugs in several different mouse cancer models—even among cells resistant to standard chemotherapy. The combination of drugs appeared less toxic than standard chemotherapy, were relatively inexpensive, and should be clinically evaluated, said Dwayne G. Stupack, PhD, the study's senior author and Associate Professor in the Division of Gynecologic Oncology at Moores Cancer Center.

With further work, said the authors, this finding could lead to new approaches to treat chemotherapy-resistant disease, and could enhance treatment of other cancers as well. "Our study suggests that a roadmap of targetable genetic changes in tumors should not be limited to mutations," said Stupack. "HAPTRIG may reveal additional targetable pathways across cancer types. We have provided a free web tool to allow the community to easily perform a HAPTRIG analysis on 21 cancer types."​