Early detection of childhood eye cancer doesn’t always improve survival or prevent eye loss

For the most common form of childhood eye cancer, unilateral retinoblastoma, shortening the time from the first appearance of symptoms to diagnosis of disease has no bearing on survival or stage of the disease, according to a study by researchers at Columbia University Mailman School of Public Health in partnership with the Hospital Infantil de Mexico. The results appear online in the journal Cancer Epidemiology, Biomarkers & Prevention.

Because retinoblastoma is easily detectable by shining a light into a child’s eye—often as a “cat’s eye” reflection revealed through flash photography—a number of countries, particularly resource-poor countries where the disease is more prevalent, have initiated education and screening programs, thinking that catching the disease early would lead to improved outcomes. This study is the first to follow a cohort of children with the disease over time and to look at the unilateral (one eye) and bilateral (two eyes) forms of the disease separately.

Our study suggests that screening children for retinoblastoma may not improve outcomes for the majority of patients, particularly for the more common form of the disease affecting one eye,” says senior author Manuela A. Orjuela, MD, ScM, assistant professor of pediatrics and environmental health sciences at Columbia University Medical Center. “By the time the tumor is visible in the child’s eye, vision is infrequently salvageable, and removal of the eye is usually necessary to prevent spread of the disease.”

The research team followed 179 children with retinoblastoma in Mexico City and interviewed their parents about symptoms and socio-demographic factors. Physicians at the Hospital Infantil de México assessed disease stage using several validated methods. The researchers found that for unilateral disease, the lag-time between when parents first noticed the disease and when the children were diagnosed had no bearing on disease stage or survival. In the rarer bilateral disease, a longer lag-time was strongly associated with a more advanced stage and worse survival, but it did not predict the extent of disease involvement in the more affected eye. Lag-times averaged seven and eight months for unilateral and bilateral disease, respectively.

Retinoblastoma is usually thought of as one disease. But there is good evidence that unilateral and bilateral retinoblastoma are distinct and progress in different ways,” says Dr. Orjuela.

There is also significant variation in how tumors respond to treatment, no matter how soon we initiate therapy,” says first author Marco A. Ramírez-Ortiz, MD, chief of the department of Ophthalmology at the Hospital Infantil de México Federico Gomez, Mexico City.

Education and Housing Conditions Predict Outcomes

Intriguingly, the researchers found that stage and survival in both forms of retinoblastoma were predicted by the mother’s education level. Mothers with less formal schooling had children with significantly higher stage disease and significantly worse survival. Education was more important than the time needed for families to travel to the hospital or how many other young children needing childcare were in the household.

The child’s home environment may be another contributing factor. Children born in homes with dirt floors had more advanced disease than their peers with different housing conditions, even after taking family income into account, says Dr. Orjuela. “There is a possibility that these children were exposed to metal or some other toxin in the dirt, although confirming this hypothesis would be difficult, given the rarity of the disease.”

The finding on maternal education may offer a more fruitful intervention. “We may need to rethink the costs and benefits of screening programs and consider how to improve survival among children with less-educated parents,” says Dr. Orjuela.

Although pathologic stage and tumor histology are important in the diagnosis and prognosis of retinoblastoma, social factors can help us gain new insights into how the disease progresses and, eventually, new ways to prevent and treat it,” says co-author Lourdes Cabrera-Muñoz, MD, Departamento de Patologìa, Hospital Infantil de Mèxico, Mexico City.

This work represents the latest finding from a longstanding multi-institutional collaboration involving co-authors Aurora Medina-Sansón and M. Veronica Ponce-Castañeda at the Hospital Infantil de México Federico Gomez, Mexico City; and Xinhua Liu at the Mailman School.

Ramírez-Ortiz et al., (2014). Diagnostic delay and socio-demographic predictors of stage at diagnosis and mortality in unilateral and bilateral retinoblastoma. Cancer Epidemiol. Biomarkers Prev., EPub Ahead of Print, doi: 10.1158/1055-9965.EPI-13-1069 [Abstract]

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Health gap between adult survivors of childhood cancer and siblings widens with age

Long-term follow-up of adult survivors of childhood cancer reinforces need for lifelong health surveillance for childhood cancer survivors

Adult survivors of childhood cancer face significant health problems as they age and are five times more likely than their siblings to develop new cancers, heart and other serious health conditions beyond the age of 35, according to the latest findings from the world’s largest study of childhood cancer survivors. St. Jude Children’s Research Hospital led the research, results published online in the Journal of Clinical Oncology.

The federally funded Childhood Cancer Survivor Study (CCSS) found that the health gap between survivors and their siblings widens with age. Survivors who were 20 to 34 years old were 3.8 times more likely than siblings of the same age to have experienced severe, disabling, life-threatening or fatal health conditions. By age 35 and beyond, however, survivors were at five-fold greater risk.

By age 50, more than half of childhood cancer survivors had experienced a life-altering health problem, compared to less than 20 percent of same-aged siblings. More than 22 percent of survivors had at least two serious health problems and about 10 percent reported three or more. The problems included new cancers as well as diseases of the heart, lungs, liver, kidneys and hormones.

Survivors remain at risk for serious health problems into their 40s and 50s, decades after they have completed treatment for childhood cancer,” said first and corresponding author Gregory Armstrong, M.D., an associate member of the St. Jude Department of Epidemiology and Cancer Control. “In fact, for survivors, the risk of illness and death increases significantly beyond the age of 35. Their siblings don’t share these same risks.

Among survivors who reached age 35 without serious health problems, 25.9 percent developed a significant health problem in the next decade. In comparison, 6 percent of siblings developed their first serious health condition between the ages of 35 and 45.

The study involved 14,359 adult survivors who were treated for a variety of pediatric cancers at one of 26 U.S. and Canadian medical centers. The research also included 4,301 siblings. For this study CCSS investigators focused on 5,604 survivors who have now aged beyond 35 years. The results provide the broadest snapshot yet of how the first generation of childhood cancer survivors is faring as they age. The oldest survivors in this study were in their 50s.

The findings highlight the importance of lifelong, risk-based health care for childhood cancer survivors, Armstrong said. Depending on their cancer treatment and other risk factors, follow-up care may include mammograms and other health checks at a younger age than is recommended for the general public. These screenings are designed to identify health problems early when there is a greater chance to prevent illness and preserve health.

Today, St. Jude researchers are studying strategies to educate and empower survivors to ensure they receive recommended screenings. Screening guidelines were developed by St. Jude and other members of the Children’s Oncology Group (COG), which includes pediatric cancer researchers and institutions around the world.The importance of such efforts is expected to grow along with the nation’s population of childhood cancer survivors. The U.S. is now home to more than 363,000 pediatric cancer survivors. An overall long-term pediatric cancer survival rate of 80 percent means the number of survivors will increase.

The study also adds to evidence that some survivors experience accelerated aging, possibly due to their cancer treatment. Researchers are still trying to identify the cause. In this study, 24-year-old childhood cancer survivors and their 50-year-old siblings reported similar rates of severe, life-threatening or fatal health problems.

This study involved survivors whose cancer was diagnosed between 1970 and 1986 when they were age 20 or younger. All survived at least five years. Since then, cancer therapies have evolved and include less radiation and chemotherapy, both of which can have long-term health consequences. The CCSS is also studying the health of adult survivors from a more recent treatment era.

Armstrong et al., (2014). Ageing and risk of severe, disabling, life-threatening, and fatal events in the Childhood Cancer Survivor Study. J. Clin. Oncol., doi: 10.1200/JCO.2013.51.1055 [Abstract

Primary androgen deprivation therapy ineffective for most men with early prostate cancer

A study of more than 15,000 men with early stage prostate cancer finds that those who received androgen deprivation as their primary treatment instead of surgery or radiation did not live any longer than those who received no treatment.

The research team, led by scientists at Georgetown Lombardi Comprehensive Cancer Center, say that the risks of serious adverse events associated with the treatment — which has been linked to impaired cognition, heart disease, diabetes and other disorders — “mitigates against any clinical or policy rationale for use of primary androgen deprivation therapy in these men.

The findings, reported Monday in the Journal of Clinical Oncology, draw from cancer registries linked with extensive electronic medical records in three, large integrated health plans. The men included in the study had prostate cancer that had not spread beyond the organ (localized) and did not have surgery or radiation therapy, considered curative treatment.

Androgen deprivation therapy suppresses the production of testosterone, the male hormone said to fuel growth of prostate cancer. The therapy improves survival when given with radiation for later stages of disease, and is considered the standard of care for men who have metastatic prostate cancer. Effectiveness of primary androgen deprivation therapy (PADT) has not been established.

This study is the most comprehensive study on the effectiveness of PADT for men who forgo radiation and surgery for their localized prostate cancer, and it tells us there is no strong reason to use it in most patients,” says the study’s lead investigator, Arnold Potosky, PhD, a professor of oncology and director of health services research at Georgetown Lombardi. “We found only a small survival benefit for primary androgen deprivation therapy compared to no therapy in men diagnosed with higher-risk localized prostate cancer.

Use of primary androgen deprivation therapy for early stage prostate cancer is widespread. Despite the lack of randomized clinical trials to test its effectiveness, recent studies have reported it as the second most common treatment, after radiotherapy, for clinically localized prostate cancer among older men age 65 and older. The study did not compare androgen deprivation therapy directly to either surgery or radiation therapy, the two main curative treatment options for prostate cancer.

While the study did not probe the reasons why physicians prescribe the treatment in this setting, it was much more common in older men and those with higher risk of disease progression. Potosky speculates that men and their doctors may feel the treatment is a useful option to delay progression of prostate cancer for men who are not good candidates for, or who prefer to avoid, surgery or radiation due to their side-effects.

Primary androgen deprivation therapy may be preferable to some men with early stage prostate cancer who would prefer to do something rather than watch and wait for further signs of progression to occur later and then need treatments,” Potosky adds. “However, using PADT by itself immediately after diagnosis in the hopes of limiting cancer’s progression does not extend survival, according to this study.”

The researchers are now using their database of 15,170 patients to examine rates of potential side effects from the treatment.

Given the ageing American population, more men are likely to be faced with prostate cancer so its is very important to understand the whether the risks of primary androgen deprivation therapy outweigh the survival benefit,” he says. “Ultimately, this is a decision for men and their doctors to make together, and we hope that our study provides some helpful information to guide these decisions.”

Potosky et al., (2014). Effectiveness of primary androgen-deprivation therapy for clinically localized prostate cancer. J. Clin. Oncol., EPub Ahead of Print, doi: 10.1200/JCO.2013.54.2043 [Abstract]

Social network may improve care for cancer patients

Several chemotherapy patients at the UC Davis Comprehensive Cancer Center will be invited to use tablets with a unique social networking tool as part of their treatment plan. Researchers at the Betty Irene Moore School of Nursing at UC Davis hope to prove that mobile health technology improves the care experience for patients as well as the quality of care while also reducing cost.

The project is part of a two-year, $199,854 grant from the McKesson Foundation and its national Mobilizing for Health Initiative. Research on mobile health technology in cancer care is new, said Jill Joseph, the associate dean for research at the nursing school. Other cancer-related mobile applications are available, but are limited to education and awareness and don’t provide disease management tools or real-time communication.

We have ample evidence that cancer patients often receive fragmented care, experience significant distress, and may needlessly require care in emergency departments or inpatient settings, particularly during chemotherapy,” Joseph said. “Little research and development has focused on providing novel technologies to support cancer care coordination.

Participating patients will use a tablet device, such as a Google Nexus or iPad, to connect to their unique and private Personal Health Network that includes a nurse coordinator — who manages the their care — along with family, caregivers, clinicians and other desired partners. These people can connect with one another through real-time messaging, video and audio components as well as schedule appointments, assign tasks, store and track information and more.

A nurse coordinator is assigned to support each chemotherapy patient who uses the mobile application. This coordinator monitors the patient’s care plan, triages issues and communicates with caregivers. Unlike electronic health records and other information systems common in hospitals, the social networking platform allows patients, their families and caregivers to not only access information but communicate with another and make decisions about care and health management.

This is a new tool designed with the patient and family at the center of care,” said Katherine Kim, a recent doctoral graduate of the UC Davis nursing school who is now a visiting faculty member and project director.

For example, a chemotherapy patient might message her nurse coordinator that she’s not doing well that day, and feels nauseous and anxious. The nurse can then communicate with the patient to further assess the situation, communicate with other caregivers, and work with the patient to address the issues or take other steps such as reschedule appointments or review current medications.

Developed by private technology partner Tiatros, the social networking platform is different from other social media sites, like Facebook and LinkedIn, because it complies with health privacy laws and operates securely.

I’m excited about bringing nursing research into the Cancer Center. I’m especially excited for our patients to have an opportunity to be part of this project,” said Kerri Stuart, a nurse manager at the Cancer Center. “Learning you have cancer is overwhelming and the thought of chemotherapy is often terrifying. This is a tool that empowers patients and provides access to information when they need it, not just when the clinic is open.

Research team members will interview patients after they have used the program for six months to determine how their health, the delivery of care and their need for emergency or inpatient care was affected. The team includes nursing faculty from the School of Nursing as well as oncology nurses, social workers, and physicians from the UC Davis Comprehensive Cancer Center.

The study is the first funded project resulting from the development of the UC Davis Collaborative Cancer Care Research Group, a multidisciplinary team of experts who hope to develop technology-enabled solutions that improve the quality, accessibility and affordability of cancer care.

Young survivors of skin cancer at risk of developing other cancers

Risk decreased significantly with increasing age, but it remains higher compared with individuals who have never had non-melanoma skin cancer (NMSC).

NMSC is considered the most common type of skin cancer, relatively easy to treat if detected early, and rarely spreading to other organs. “Our study shows that NMSC susceptibility is an important indicator of susceptibility to malignant tumors and that the risk is especially high among people who develop NMSC at a young age,” said Professor Sinclair, Professor of Medicine at the University of Melbourne and Director of Dermatology at Epworth HealthCare.

The researchers collected hospital admission and death data from the All England Record-linked Hospital between 1999 and 2011, and constructed two cohorts: a cohort of 502,490 people with a history of NMSC, and a cohort of 8,787,513 people who served as controls. The risk for developing any cancer subsequent to NMSC decreases significantly with increasing age: 23 times higher risk for those under 25 years of age; 3.52 for those 25-44 years of age; 1.74 for those 45- 59 years of age; and 1.32 for those older than 60 years. Results are published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

They followed up the participants for five to six years, 67,148 from the NMSC cohort and 863,441 from the control cohort subsequently developed cancers.

They found that for those who had NMSC, the relative risk for developing cancers of the bladder, brain, breast, colon, liver, lung, pancreas, prostate, and stomach remained consistently elevated for the entire period of the study, and the risk for cancers of the brain, colon, and prostate increased with time.

The researchers also found that those who had NMSC under 25 years of age were 53 times more likely to get bone cancer, 26 times more likely to get blood cancers, 20 times more likely to get brain cancer, and 14 times more likely to get any cancer excluding those of the skin.

The risk increases for a large group of seemingly unrelated cancers; however, the greatest risk relates to other cancers induced by sunlight, such as melanoma.”

Early detection of cancers through screening of asymptomatic people works best when screening can be targeted at those at greatest risk. Our study identifies people diagnosed with NMSC at a young age as being at increased risk for cancer and, therefore, as a group who could benefit from screening for internal malignancy,” Professor Sinclair said.

Ong et al., (2014). Subsequent primary malignancies in patients with nonmelanoma skin cancer in England: A national record-linkage study. Cancer Epidemiol. Biomarkers Prev., 23: 490-498 [Abstract]

Older people not receiving adequate access to cancer care

Older people all around the globe are being denied proper access to cancer care, according to an editorial by Queen’s University Belfast academic, Professor Mark Lawler of the Centre for Cancer Research and Cell Biology.

In an editorial in the BMJ (British Medical Journal) Professor Lawler said: “there is increasing evidence from around the world that elderly patients are being ‘undertreated’, leading to a ‘survival gap’ between older and younger patients.

We need a fundamental change in cancer policy for the elderly patient. Our current practices are essentially ageist, as we are making judgements based on how old the patient is rather than on their capacity to be entered into clinical trials or to receive potentially curative therapy. It is disappointing that we see different principles being applied for older patients when compared to younger patients, with these differences leading to poorer outcomes in the elderly patient population.”

Professor Lawler’s findings are published in an editorial in the BMJ entitled, ‘Ageism In Cancer Care: We Need to Change The Mindset‘. It states the need to redress the disparities in the policy on cancer for older patients, citing a recent position paper from the European Organisation for Research and Treatment of Cancer, the Alliance for Clinical Trials in Oncology and the International Society of Geriatric Oncology recommending that clinical trials should be without an upper age limit.

A high proportion of older women with a certain form of breast cancer (‘triple negative’) receive less chemotherapy than their younger counterparts – despite evidence of the treatment’s efficacy in this patient cohort, the authors claim.

They also point out that more than 70 per cent of deaths caused by prostate cancer occur in men aged over 75 years, who usually have more aggressive disease. Few older patients, however, receive treatment for localised prostate cancer, and in most cases they are denied access to chemotherapy for advanced disease, they add.

Colorectal cancer is another disease of older people, yet the evidence again suggests that optimal treatment is not being provided to this patient cohort,” Professor Lawler continues.

The paper sets its argument within the context of an ageing society – both locally and globally. Estimates for the UK suggest that 76 per cent of cancers in men and 70 per cent of cancers in women will occur in the over-65 population by 2030.

In the US, the number of over-65s is set to double at least, from around 40 million in 2009 to 89 million in 2050. Cancer is mainly a disease of the elderly. Given our ageing demographic, the paper argues, this will lead to an exponential increase in the number of cancer deaths unless we change our approach towards the elderly cancer patient.

The International Cancer Benchmarking Partnership – a collaboration that compares clinical outcomes between Australia, Canada, Denmark, England, Northern Ireland, Norway, Sweden and Wales – has indicated decreased survival for patients older than 65 years. A EUROCARE 5 study confirmed this trend, suggesting that the survival gap was widening between older and younger patients in Europe.

The evidence provided highlights the ‘urgent need’ for a ‘geriacentric’ strategy that maximises clinical trial activity in older patients, makes existing treatments more available and develops new approaches that are well tolerated in older people, the paper says in its closing comments.

Professor Lawler concludes: “Such a strategy will also have to ensure that the principle of early diagnosis (underpinning more effective and less aggressive treatment) is applied in older patients as well as in their younger counterparts. Only then can we truly deliver a comprehensive cancer service to the elderly population in our society.

Lawler et al., (2014). Ageism in cancer care: We need to change our mindset. BMJ348:g16  doi: http://dx.doi.org/10.1136/bmj.g1614 [Abstract]