The use of real-time comprehensive profiling provides valuable diagnostic information and identifies potential therapeutic targets in adults with malignancies, but this process remains widely underutilized for pediatric patients and represents a significant unmet need. Investigators in Heidelberg, Germany, using the INFORM (INdividualized therapy FOr Relapsed Malignancies in Childhood) registry demonstrated the feasibility of implementing a large-scale multinational personalized oncology platform to aid in decision-making and improve clinical benefit. INFORM also provided diagnostic refinement and targeted therapy options to pediatric patients.

“This is the first time that such a large precision oncology platform [involving] pediatric patients was assessed for its clinical benefit,” Cornelis M. van Tilburg, MD, PhD, senior physician in Pediatric Oncology and Hematology, and head, Early Phase Clinical Trials at the Hopp Children's Cancer Center, in Heidelberg, Germany, said during a press program ahead of the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

Eight countries participated in the study by sending samples from pediatric patients for molecular analysis. The analyses were shared with an online interdisciplinary molecular tumor board that included the patient’s pediatric oncologist. A predefined algorithm using a 7-step scale that ranged from “very high priority” to “very low priority” target labels was implemented and was based on how druggable the target was, the alteration type, and any specific evidence. Treating physicians could access an online database to review the analyses.

“It is important to note that INFORM is not a clinical trial,” Tilburg said. “Treatment decisions made by the patient’s physician encompassed either enrolling the pediatric patient in a clinical trial, prescribing an off-label targeted drug, or treating with conventional therapy.” Any documentation follow-up was included in the online database.

In the analysis presented at ASCO, samples from 526 children were evaluated, of which 149 received a matching targeted drug. Twenty samples were determined to have the highest priority label. Children with higher-level targets more frequently received a matching targeted drug, said Tilburg. Seventeen children (3.2%) enrolled in clinical trials and 40 children (7.6%) with a potential cancer predisposition syndrome were detected, 17 of which were previously unknown. Families of these children were offered genetic counseling. “In approximately 8% of the brain tumors, we were able to provide diagnostic refinement of the original diagnosis,” Tilburg said.

Progression-free survival (PFS) rates in patients who received a matching targeted drug were similar to patients who did not receive a matching targeted drug. The survival curves overlap, said Tilburg.

An analysis of the highest priority level targets, however, reveals that those patients who had a very high priority level target and received a matching targeted drug had a median PFS rate of 204.5 days, compared with all other children, whose PFS rate was 114.0 days. “Children with very high priority level target show longer PFS,” Tilburg said.

In the initial INFORM study, 214 tumor samples of pediatric patients at high-risk were profiled and collected from 47 German centers.

 A breakdown of tumor types revealed that 39% were sarcomas, 30% were brain tumors, 13% were neuroblastomas, and 18% were hematological or other malignancies. On average, the turnaround time from tissue arrival to molecular results was 21 calendar days. In 14 of 214 patients (7%), the investigators identified an underlying germline predisposition syndrome. The investigators detected 1 or more potentially druggable alterations in 69% of samples (147 out of 214). Based on these findings, targeted therapeutics were incorporated into the therapy regimen in one-third of patients.

Tilburg said that pediatric precision oncology in a real-world, multinational setting is feasible. For the subgroup of children with very high priority level targets, the INFORM registry provided therapeutic opportunities and new diagnostic information.

“Looking to future research, there is an urgent need for biomarker-driven pediatric interventional clinical trials,” Tilburg said. “A significant group of patients didn't have very high-level targets and we should put our efforts in adding additional layers of diagnostics to allow them to benefit from new treatments,” he concluded.

1. Van Tilburg CM. The pediatric precision oncology study INFORM: Clinical outcome and benefit for molecular subgroups. J Clin Oncol. 2020;38(suppl; abstr LBA10503). doi: 10.1200/JCO.2020.38.15_suppl.LBA10503           

2. Worst BC, Pfaff E, Van Tilburg CM, et al. The INFORM personalized medicine study for high-risk pediatric cancer patients. J Clin Oncol. 2017;35(suppl 15):10509-10509. doi: 10.1200/JCO.2017.35.15_suppl.10509

This article was originally published on OncLive as, "

Using a Multinational Pediatric Cancer Registry Helps to Improve PFS in High-Risk Patients

Articles

Pediatric precision oncology in a real-world, multinational setting is feasible. For the subgroup of children with very high priority level targets, the INFORM registry provided therapeutic opportunities and new diagnostic information.
 

International Pediatric Cancer Registry Can Improve Outcomes

A study by researchers with the US Department of Defense Center for Prostate Disease Research (CPDR) Multicenter National Database has found that for men with positive needle biopsy for prostate cancer, active surveillance (AS) did not negatively impact their quality-of-life compared with men who had a negative prostate needle biopsy.

These findings suggest that a more conservative treatment approach was not a stress point for these individuals with low-risk disease.

“We found that there were really no quality-of-life differences between these two groups of men, which was a nice surprise,” said lead author Jennifer Cullen, PhD, MPH, director of the CPDR Epidemiological Research Program. “We were concerned that those who had cancer would have worse mental health, because of a confirmed cancer diagnosis.”

The findings suggest that AS “is a reasonable option in low-risk patients in terms of promoting and maintaining a high level of quality of life relative to those patients without cancer,” Cullen said.

Data for the years 2007-2014 were evaluated. Of the 1204 individuals who met study eligibility requirements, 420 (35%) had a negative prostate needle biopsy (noncancer group) and 787 (65%) had a positive prostate needle biopsy for cancer. Of the men with a positive finding, 411 (52%) were diagnosed with low-risk prostate cancer, 89 of whom were placed on AS.

Cullen and researchers used two questionnaires with established validity and reliability—EPIC, a prostate cancer specific instrument, and SF-36, a general health assessment test to determine health-related quality-of-life (HRQoL) measures. Findings were assessed at biopsy (baseline) and annually for up to 3 years. The researchers said they undertook the study because it is poorly understood how HRQoL of men who select AS compares with the HRQoL of men at similar risk, but without prostate cancer.

“In our study, we focused on two patient subsets—one group that was biopsied was found to not have cancer. The other group had cancer but was at such low risk that it was a comfortable option for the physician to advise the patient that he was eligible for active surveillance,” said Cullen, a research assistant professor in the department of surgery at the Uniformed Services University of the Health Sciences.

EPIC measures four paired subscales: urinary, sexual, bowel, and hormonal function and bother. SF-36 measures eight subscales that can be combined into physical and mental component summary scores. Both tests offer subscale scores that range from 0 to 100, with higher scores indicating better HRQoL. HRQoL surveys were administered before or after biopsy (baseline), and at 3, 6, 12, 18, 24, 30, and 36 months after a positive biopsy or 12, 24, and 36 months after a negative biopsy. The researchers reported that only baseline surveys and those from 12-, 24-, and 36-month points were included in the analysis.

The researchers found that the only time HRQoL trends differed were for urinary function and mental health subscales, with the group undergoing AS reporting additional decreases of approximately two points per year. Cullen and colleagues attributed this finding as a regression to the mean, particularly with regard to urinary functions, which was higher in the AS group at baseline. They reported that the changes did not result in statistically significant or clinically meaningful differences in adjusted mean scores of these subscales at 3 years.

The decision for a patient to choose active surveillance is a complex one, said Cullen. “A number of factors go into the decision. It could be that the physician strongly recommends it, the patient may have a preference to avoid surgery or radiation therapy, or the patient’s spouse might recommend against surgery or radiation therapy.”

She added that surgery and radiation can result in sexual, urinary, and bowel dysfunction, “so there are serious consequences in pursuing aggressive treatment. A man in his 50s or 60s may want to delay treatment because of those adverse events that affect these core functions,” she said.

The interplay between patient and clinicians is important, and Cullen pointed out that “all of the patients who participated were seen in a multidisciplinary clinic where they have a chance to meet with a radiation oncologist, surgical oncologist, and even a nurse educator.” All the health team members had a chance to meet, and all treatment options were on the table, she said.

However, this setting could have biased the results, she cautioned, because the general population does not always have the same level of access to healthcare facilities and consistency in follow-up care, as in the military population who participated in the study. In addition, armed forces personnel tend to be “very loyal to this health system, so we don’t see the high rates of attrition that might occur outside of this military cohort.”

“We know overwhelmingly that most men with a prostate cancer diagnosis are going to have a positive outcome. I’m confident in saying that their quality of life remains high during the 3-year period after diagnosis,” she said. “But because this is one study that examined one military cohort, more studies should be undertaken to repeat the analysis,” Cullen concluded.

 Pham KN, Cullen J, Hurwitz LM, et al. Prospective quality of life in men choosing active surveillance compared to those biopsied but not diagnosis with prostate cancer. 

For men with positive needle biopsy for prostate cancer, active surveillance (AS) did not negatively impact their quality-of-life compared with men who had a negative prostate needle biopsy.

For Men With Low-Risk Prostate Cancer, Active Surveillance Does Not Cause More Stress

Although use of robotic surgery for prostate cancer has surpassed open surgical procedures, the impact of this approach on patient quality of life has not been well-studied. To address this knowledge gap, a group of researchers compared quality of life (QOL) indicators from two prior studies of patients with prostate cancer who had either robotic or open surgery and found that scores on sexual function were better for those who had the robotic procedure, yet comparative results for urinary function were not as conclusive.

The findings of the analysis were shared in a late-breaking abstract reported at the 2015 American Urological Association (AUA) Annual Meeting May 17, 2015 in New Orleans.

“In our study, we examined urinary and sexuality quality of life outcomes from two large cohort studies that were separated in time and dominated by a single technique,” said Brock O’Neil, MD, of the department of Urologic Surgery at the Vanderbilt University Medical Center. “Our hypothesis was that neither surgical approach would result in superior quality of life over the other.”

Currently most available QOL data on robot-assisted, laparoscopic radical prostatectomy (RALP) and open radical prostatectomy (RRP), are from single surgeon/center reports, lack adequate risk-adjustment, or use limited information on patient-reported outcomes, O’Neil explained.

To gain a better comparative understanding of post-prostatectomy QOL, researchers looked at data from two large, population-based, prospective cohort studies: the Prostate Cancer Outcomes Study (PCOS) conducted from 1994-1995 and the more recent Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study which was carried out from 2011-2012. All PCOS patients had open surgery, and QOL was assessed using the UCLA Prostate Cancer Index. The majority of men (78%) in CEASAR had the robotic procedure, and QOL was measured using the Expanded Prostate Cancer Index Composite-26.

In order to account for differences in these tools, researchers identified four common measures of urinary incontinence, three of sexual function, and set modified domain summary scores on a scale of 0-100, with 100 indicating ideal function.

Differences between the groups were assessed at 6 and 12 months after surgery using multivariate linear regression. Covariate adjustment was used to control for sociodemographic and clinical pathologic features, including baseline urinary and sexual function.

Data were analyzed for 2438 men across the two study cohorts, 1505 of whom had RRP, and 933 had RALP. Among the men who underwent RRP, 1243 were from the PCOS study and 262 were from the CEASAR study.

For the 74% of men with excellent urinary function scores (= 100) at baseline, those who underwent RALP had a mean QOL score of 74.1 at 6 months versus 70.4 in the RRP group (a difference of 3.8 points, 95% CI, 1.1-6.4); however, urinary continence scores were not significantly better at 12 months (78.7 vs 77.5, respectively, or a difference of 1.2 points; 95% CI, -1.3- 3.7).

Among the upper quartile of men who had with excellent baseline sexual function, the mean score after 6 months was 55.1 in the RALP group versus 44.9 in the RRP cohort, a difference of 10.2 points (95% CI, 7.5-12.9). Notably, and unlike the urinary continence scores, at 12 months, the sexual function score differential was sustained, with better scores in the robotic surgery group (61.4 vs 51.1, respectively, a 10.3-point difference; 95% CI, 7.5-13.1).

In the lower quartile of men with reduced sexual function at baseline (score = 65) the mean score for those undergoing robotic surgery still had a statistically significant better score (45.9 vs 40.7, respectively (+5.2 [95% CI,2.8-7.6]) which continued at 12 months, where mean scores were 3.3 points higher in the RALP group (49.0 vs 45.7, respectively [95% CI, 0.8-5.8]).

“Sensitivity analysis, which compared robotic CEASAR vs open CEASAR, robotic CEASAR vs open PCOS, and open CEASAR vs open PCOS, provided consistent support for the sexual function outcomes and mixed support for urinary incontinence outcomes,” said O’Neil.

O’Neil noted that the study had a few limitations. QOL measures were used from two different scales, which were not previously psychometrically validated, and PDE5 inhibitors were not available during the PCOS enrollment period.

“Our study, using CEASAR and PCOS, which were performed more than a decade apart but having similar methodology, suggests that robotic surgery performs better than open surgery for sexual function and possibly urinary function, out to at least 12 months,” O’Neil concluded.

Longer follow-up is required to establish whether benefits persist beyond 1 year and to assess for differences in oncologic outcomes.

	O'Neil B, Koyama T, Rudd J, et al. Evidence of superior quality of life after robotic prostatectomy: results from a population-based analysis. Presented at: AUA Annual Meeting; May 15-19, 2015; New Orleans, LA. Abstract PII-LBA5.

Although use of robotic surgery for prostate cancer has surpassed open surgical procedures, the impact of this approach on patient quality of life has not been well-studied. 

Measuring Quality of Life After Robotic Surgery for Prostate Cancer

When the United States Preventive Services Task Force (USPSTF) recommended against routine PSA screening for early detection of prostate cancer in May 2012, it caused a sea change in practice patterns among primary care physicians.

The impact of the recommendations had “a significant chilling effect,” said Sam Chang, MD, a professor of Urology at Vanderbilt University Medical Center, who moderated a panel discussion on the topic at the 2015 American Urological Association (AUA) Annual Meeting.

Data presented by Ryan Werntz, MD, during the panel discussion showed that after the guideline was issued, the overall rate of PSA testing decreased by 50% among primary care physicians at Oregon Health & Science University (OHSU).

In particular, the most significant decrease in PSA use was seen in men aged 50 to 70 years—a cohort most likely to benefit from screening.

“If you look back before PSA was a big part of prostate cancer screening, 20% to 25% of men would often first see a physician with back pain and be subsequently diagnosed with metastatic disease,” said Werntz, a urologic resident at OHSU.

“It’s a little bit unnerving, because if the guidelines for primary care physicians are recommending not to screen for prostate cancer, we could go back to those days when 1 in 5 men are presenting with metastatic disease,” continued Werntz. “Now, only 4% of men are presenting with metastatic disease, and that has to be due to PSA screening.”

Previous research revealed a significant decrease in screening frequency in two cohorts of men studied from June-November 2011 and during the same 6-month period in 2012 after the USPSTF guideline (8.6% vs 7.6%, 

 = .0001; adjusted odds ratio 0.89; 95% CI, 0.83-0.95).

The goals of the study reported at AUA were to identify trends in PSA testing by OHSU primary care physicians before and after the recommendation was issued, to determine which age groups were impacted the most, and to identify the rate of PSA testing in men with lower urinary tract symptoms (LUTS). The USPSTF guideline was largely based on an analysis from the Pacific Northwest Evidence Based Practice Center at OHSU, noted Werntz.

Men aged >40 years who were new patients at the family or internal medicine clinic at OHSU between January 2008 and December 2013 were identified for inclusion in the study using the OHSU electronic database. Those with a history of prostate cancer or who had previously been treated by a urologist were excluded.

Researchers compared PSA testing before and after the USPSTF recommendation, with results stratified by age. They found that PSA testing for men aged 50-59 years fell from 19.2% over the 4 years 2008-2012 before the USPSTF recommendation, to 8.5% after May 2012 when the guideline was issued—a reduction in screening of 56%. Similarly, for men aged 60-69 years, the rate fell by 60%, from 19.3% to 7.2%, respectively.  

The researchers observed no significant difference in the frequency of PSA testing for men aged 40 to 49 years after the recommendation was issued (4.2% vs 4.4%, respectively) and for men 70 years or older (10.2% vs 9.3%, respectively).

Benign prostatic hyperplasia (BPH) or LUTS was a noted diagnosis in 3.6% of new patients examined, yet only 36% of men with this diagnosis were given a PSA test, suggesting underutilization of PSA in this symptomatic group of men. LUTS is a potential symptom of advanced prostate cancer, but current AUA guidelines suggest that PSA testing is optional. AUA guidelines do recommend a digital rectal exam (DRE), but this is often not done, Werntz noted.

Widespread use of PSA testing has contributed to the detection and overtreatment of men with low-risk, non-aggressive prostate cancer. Nevertheless, recognizing the benefits of PSA testing, the AUA updated its guidelines in 2013 to incorporate a man’s health risk, age, race, and family history.

Enhanced education for primary care providers is required to stress that not every prostate cancer needs treated. Screening should include shared decision making with the patient and a restriction of screening and biopsy to high-risk groups of healthy men. For those at low-risk, less frequent PSA screening could be appropriate and newer tests that correlate with cancer aggressiveness could be utilized to lessen the chance of overdiagnosis and overtreatment.

“Urologists are uniquely positioned to monitor PSA test results with their patients, and to know when to biopsy an individual,” concurred Werntz. “Obviously, it should be a shared decision.”

			Werntz R, Martinez-Acevedo AC, Conlin MJ, et al. Trends in PSA utilization by primary care physicians: impact of the USPSTF recommendation. Presented at:  AUA Annual Meeting; May 15-19, 2015; New Orleans, LA. Abstract PD44-02.

			Cohn JA, Wang CE, Lakeman JC, et al. Primary care physician PSA screening practices before and after the final US Preventive Services Task Force recommendation. 

PSA Screening Declines, Especially Among Men Most Likely to Benefit

A new study has found that older, single white males with advanced bladder cancer have the highest suicide risk among those with other cancers of the male genitals and urinary system. 

“The older, white, single male is already at higher risk in the general society for suicide; add on the fact that he has advanced bladder cancer, and this is a high-risk patient,” said Zachary Klaassen, MD, a urology resident at the Medical College of Georgia at Georgia Regents University, the study’s corresponding author. “But this has taught me that we have to look for warning signs in all these patients.”

When compared with the general population, overall suicide risk was 2.7 times higher for bladder cancer patients; rates were 1.86 times higher in kidney cancer patients, 1.27 times higher in prostate cancer, 1.23 times higher in testicular cancer, and 0.96 times higher in penile cancers.

Researchers reviewed the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, or SEER, database from 1988-2010 to find 1.2 million people with genitourinary cancer, examining variables such as age, sex, race, as well as disease and treatment aggressiveness.

They found that bladder cancer patients across the board, whether or not they had surgery or advanced disease, had a higher suicide risk than patients with other genitourinary cancers. Older patients with bladder, prostate, and testis cancer were generally at an increased risk. When looking specifically at the black population, those with bladder cancer also had the highest suicide rates; however, those with bladder, prostate, and kidney cancer had much lower suicide rates than whites in the group. Prostate cancer patients had an increased suicide risk over time, with the highest rate 15 years or more after their diagnosis.

The review identified suicide in these patients as a public health dilemma that needs physician awareness, particularly in patients who are older, male, and have aggressive disease.

“It’s a tough situation. We have to talk more with our patients about how they are feeling even if it’s uncomfortable for us,” said Martha K. Terris, MD, chief of the section of Urology, chief of Urology at the Charlie Norwood Veterans Affairs Medical Center, and the study’s senior author.

The clinicians recognized the challenging road faced by many of these patients during recovery. Those with bladder cancer, for example, often have surgery to both remove their diseased bladder and divert urine to a collection bag at their side. Recovery from this major procedure takes about 3 months; interferes initially with bowel function; can result in ongoing problems such as leakage and infection; and patients need long term, close follow up for signs of metastasis, so it’s also a very expensive cancer to treat.

Monica Smith, the executive director of the Bladder Cancer Advocacy Network (BCAN) says its important for patients to remember that "cancer is not a death sentence though in the debpths of depression, it may seem like it."

"Most bladder cancer patients, even those with urinary diversion, are able to maintain a full and active lifestyle and BCAN can offer support and resources that can help," she added. 

The average age of diagnosis of bladder cancer is 73, and about nine out of 10 patients with bladder cancer are over age 55, according to the American Cancer Society. Bladder cancer is more common in men and smokers, with about 74,000 new cases annually in this country and more than a half million survivors. Suicide is the 10th leading cause of death in the United States; cancer is number two, according to the Centers for Disease Control and Prevention.

Study Finds Advanced Bladder Cancer Increases Suicide Risk

The continuing contentious debate about screening for prostate cancer remains top of mind among the public and lay press, but, Leonard G. Gomella, MD, told attendees at the 8th International Prostate Cancer Congress, the decision to screen or not to screen boiled down to “using common sense, shared decision making, and choosing the right patients to screen.”

At the heart of the debate is the US Preventive Services Task Force (USPSTF) recommendation against PSA-based screening.

 The task force gave the screening test a grade D back in May 2012, but Gomella, professor and chairman of the Department of Urology at the Sidney Kimmel Cancer Center, Thomas Jefferson University, stressed that a careful reading of the full recommendation is necessary.

“If you read the fine print, the recommendation says to discuss the treatment options with your patient and that screening could be conducted on an every-other-year basis,” he said.

That’s not to say that the recommendation is not without flaws, however. “The recommendation missed some important concepts,” he continued. “It focused on complications of treatment—incontinence, erectile dysfunction, and rectal injury&mdash;but not on the value of screening and the amount it has saved the healthcare system.”

Additionally, the recommendation discussed population screening, “but ignored African Americans, the effect of family history, and morbidity associated with prostate cancer. And most importantly, no one on the task force has actually treated patients with prostate cancer,” Gomella noted. The latter point has spurred the introduction of legislation that could reform the task force by requiring consultation with experts who treat the specific disease in question.

The case for screening is a good one with 5-year relative survival in men diagnosed with prostate cancer approaching 100%, said Gomella.

 Prostate cancer mortality was on the decline before the task force issued its recommendation, but it’s not clear if screening was the sole contributor. Most likely it was “a combination of increased screening and better therapy,” he said.

But recent findings presented at the 2015 Genitourinary Cancers Symposium suggest a deleterious effect of the task force guidelines. Researchers found that between 2011 and 2013, there was a 6% increase in the diagnosis of intermediate or higher risk prostate cancer in men and concluded that many more deaths could result from this disease.

They made no determination whether a decline in PSA screening was the cause.

The results of two large screening trials

 suggest that the ideal candidates for PSA screening are men who are at high risk of prostate cancer, older men, those with a family history, those who are at high risk of suffering morbidity and mortality from the disease, and men who are in good health and are asymptomatic with a life expectancy of 10-15 years.

Other diseases experience conflicting recommendations as well, said Gomella. “Breast, lung, and thyroid cancer recommendations run into similar problems. With prostate cancer, there are many men with false negatives, but few with prostate cancer. This suggests we have to refine our screening efforts: do it smarter, do it better, and avoid overtreatment.”

One emerging tool that might help clinicians are new genomic tests, and several are currently available, including the Genomic Health Oncotype DX prostate cancer test and the Myriad Prolaris test. It is hoped that genomic tests will help stratify patients with localized prostate cancer based on disease aggressiveness. “It will become more important to incorporate these tests in deciding who is at the biggest risk for not treating early prostate cancer,” said Gomella.

Gomella recommended better education for primary care physicians because not all prostate cancer needs treatment when detected, shared decision making with the patient, restricting screening and biopsy to high-risk groups of healthy men, less frequent PSA screening if the patient is at low risk or has a low PSA, and to consider incorporating newer tests that correlate with cancer aggressiveness to lessen the chance of overdiagnosis and overtreatment.

			Moyer VA. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(2):120-134.

			H.R. 1151, The USPSTF Transparency and Accountability Act of 2015. https://www.govtrack.us/congress/bills/114/hr1151. Accessed March 14, 2015. 

			National Cancer Institute. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/statfacts/html/prost.html. Accessed March 14, 2015.

			Hall MD, Schultheiss TE, Farino G, et al. Increase in higher risk prostate cancer cases following new screening recommendation by the US Preventive Services Task Force (USPSTF). 2015 Genitourinary Cancers Symposium. J Clin Oncol. 2015;33 (suppl 7). Abstract number 143. http://meetinglibrary.asco.org/content/140836-159. Accessed March 14, 2015.

			Andriole GL, Crawford ED, Grubb RL 3rd. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310-1319.

			Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-1328.

The continuing contentious debate about screening for prostate cancer remains top of mind among the public and lay press, but, Leonard G. Gomella, MD, told attendees at the 8th International Prostate Cancer Congress, the decision to screen or not to screen boiled down to "using common sense, shared decision making, and choosing the right patients to screen."

Prostate Cancer Screening: "Yes, No, or Maybe?"

The first iteration of the American Society of Clinical Oncology’s (ASCO’s) endeavor to capture and harness big data, CancerLinQ, is scheduled for release in late 2015. Eight community oncology practices have signed on to use CancerLinQ, and ASCO expects seven large cancer centers to join the effort shortly. Once the initial rollout is complete, the electronic health records of 500,000 patients who will be represented in CancerLinQ, according to a presscast today.

These initial practices include Inova Comprehensive Cancer & Research Institute (Virginia); South Coast Centers for Cancer Care (Massachusetts); New England Cancer Specialists (Maine); Medical Oncology Hematology Consultants (Delaware); Cancer Treatment Centers of America (Pennsylvania); Marin Cancer Care (California); Space Coast Cancer Center (Florida); and Michiana Hematology-Oncology (Indiana).

Using the data found in millions of electronic health records that are stored in cancer centers, insurers, and the offices of community oncologists and hematologists is a daunting task, but to reach that goal ASCO announced that the CancerLinQ platform will use the relational database management system offered by SAP, a global software developer. The CancerLinQ platform will be powered by SAP’s big data technology called HANA.

“CancerLinQ will benefit oncologists in three ways: it will provide real-time quality feedback to oncologists, allowing them to compare the actual care they provide against guidelines. It will uncover patterns that can improve care, revealing new, previously unseen patterns in patient characteristics, treatments, and outcomes. And it will provide personalized insights to doctors, offering individualized and unbiased decision support for every patient and every type of cancer,” said Peter Paul Yu, MD, ASCO president during the presscast.

“When CancerLinQ is complete, doctors will gain insights in seconds, not years, and patients will have access to high quality care based on the most up to date findings,” said Yu.

By using CancerLinQ, these practices will be able to aggregate and analyze a wide range of data and provide reports for quality improvement. Insights gathered from the data are expected to help lay the groundwork for developing the full system, in which oncology practices across the US can participate.

“CancerLinQ is intended to improve care everywhere,” said Clifford A. Hudis, MD, FACP, during the presscast. Hudis is ASCO’s immediate past president. “It is designed to support all physicians, in all settings, so its impact will not be limited to specific providers, or narrow insurance networks, or regions of the country.”

CancerLinQ will translate the data collected from highly selective patients who have participated in clinical trials and help practicing oncologists apply that data to the patients they see every day.

“We’ll have access to real-time data as far as processes and outcomes to improve the care that we deliver to our patients. We expect to be able to track acute and long-term toxicities of chemotherapy agents. What happens to patients after they complete their therapy will be of great interest,” said Therese M. Mulvey, MD, a medical oncologist from South Coast Cancer Centers for Cancer Care.

The HANA software can manipulate the data that are collected in a number of ways. All data are stored in main memory, which enhances the speed to analyze the data and can provide the real-time insight that a busy oncologist needs when he or she is seeing a patient. In addition, HANA can collect and adjust data that are collected from multiple sources (ie, different community oncology practices).

Over time, further development and input will come from physicians, patients and experts in relevant disciplines that include quality improvement, health outcomes, epidemiology and health IT. ASCO will continue to maintain control over the data, services, and products including decision support tools and analyses. SAP will provide engineering and technical support to continue to enrich CancerLinQ’s versatility.

The first iteration of the American Society of Clinical Oncology's (ASCO's) endeavor to capture and harness big data, CancerLinQ, is scheduled for release in late 2015.

CancerLinQ to Harness Big Data, Provide Better Care for Cancer Patients 

In May 2014, ASCO issued guidelines recommending the administration of adjuvant tamoxifen for 10 years in women with stage I-III hormone receptor (HR)-positive breast cancer, based on data from the collection of 5 clinical trials. This recent issuance, along with other recommendations and guidelines, served as the backdrop for the keynote address, titled “Past as Prelude: Further Dilemmas in Hormonal Treatment of Early Breast Cancer,” delivered by Norman Wolmark, MD, during the Chemotherapy Foundation Symposium on Wednesday, November 5.

“I think it’s very worthwhile reviewing the dilemmas we now face in the adjuvant therapy of breast cancer, particularly from the trials that have emerged in the last two years,” said Wolmark, a professor and chairman of the Department of Human Oncology at the Allegheny University of Health Sciences and serves as chairman and principal investigator of the National Surgical Adjuvant Breast and Bowel Project (NSABP). “This dilemma has become exacerbated. The ovary is an enigma—how are we going to address it?”

The ASCO guideline was based on findings from the large aTTom and ATLAS phase III trials, among others. In the aTTom study, women continuing tamoxifen for 10 years had a 25% lower recurrence rate and a 23% lower breast cancer mortality rate compared with those who stopped at 5 years. In the large ATLAS trial, there was a 2.8% reduction in mortality risk for continuing treatment with tamoxifen and the rate of recurrence for those receiving tamoxifen for 10 years was 25% less compared with those receiving just 5 years of treatment.

The past NCI guidelines were established in 1995 and were distributed to every oncologist at every US hospital. They were based on results from the NSABP protocol B-14, which evaluated the administration of adjuvant tamoxifen for 5 years versus 10 years in patients with HR-positive breast cancer. This study suggested that more than 5 years of adjuvant treatment was not warranted in routine clinical practice in this patient population.

“This set us back a decade. A solid decade,” Wolmark said In reference to earlier guidelines on the use of adjuvant tamoxifen. “We had not realized that there was a rebound benefit when you stopped the tamoxifen and at a 7-year preplanned interim analysis, 5 years was better than 10. And we stopped the trial because it crossed futility limits. What a mistake. The ATLAS and aTTom trials were unencumbered by interim analysis—they plotted on and went forward, so good for them.”

Looking ahead to 2015, new guidelines about AIs and GnRH agonists are on the way, said Wolmark. Additionally, further emphasis on molecular profiling should be incorporated.

“You would think we would have learned from the past,” said Wolmark, referring to the May 2014 ASCO guidelines. “Do the guidelines apply to every patient, in this age of molecular genomics? If the data are incontrovertible and absolutely definitive, then by all means go ahead and formulate guidelines. But if the guidelines don’t take into account genomic profiling, you may miss your mark. You run the risk of paying an enormous price and setting back the art by at least a decade.”

Invoking the memory of Ezra Greenspan, MD, founder of the symposium, he wondered, “What would he have thought of the consensus guidelines issued by ASCO? Would he have been in equipoise with it? I think not. He was not prone towards hyperbole. Ezra Greenspan encouraged dialogue. He encouraged discussion. He encouraged scientific discourse,” he said.

“To make that ASCO statement without taking into account genomic profiling is far too encompassing. ASCO felt the need to publish before we had the full set of information,” Wolmark said. “Ezra’s admonitions are pertinent today as they were 3 decades ago: assess the data, analyze the permutations and combinations, factor in modern advances and then speak. Otherwise, hold your peace.”

In May 2014, ASCO issued guidelines recommending the administration of adjuvant tamoxifen for 10 years in women with stage I-III hormone receptor (HR)-positive breast cancer, based on data from the collection of 5 clinical trials. 

Adjuvant Breast Cancer Therapy Poses Challenges for Clinicians

Even though breast cancer predominantly affects white women, breast cancer outcomes are worse among black women. But a new study suggests that enrollment in a federal program may help reduce racial disparities among these patients.

Results of a large study suggest the Medicare Part D Extra Help program, which provides low-income subsidies (LIS) for medications, improves women’s adherence to hormone therapy after breast cancer surgery in all racial/ethnic groups while reducing racial/ethnic disparities.

The results of this study were presented during a press briefing today in advance of the American Society of Clinical Oncology's (ASCO) 2014 Quality Care Symposium, which takes place October 17-18, 2014.

“Patients involved in the Extra Help program had substantially higher adherence rates for hormonal breast cancer therapy when compared with women who did not receive the LIS, even when stratified by race and ethnicity,” said Alana Biggers, MD, MPH, a former internal medicine resident at the Medical College of Wisconsin in Milwaukee, and currently an assistant professor of clinical medicine at the University of Illinois-Chicago.

Black women are more likely to die from breast cancer than any other group. In addition, low socioeconomic status increases death rates regardless of race or ethnicity. Factors that add to the disparity include poor or limited access to healthcare, inadequate early screening and detection, lack of health insurance, and genetics—black women more often carry inherited mutations that predispose them to breast cancer.

Researchers collected data from 23,299 women enrolled in Medicare D who were diagnosed with breast cancer and who underwent mastectomy or breast-conserving surgery between 2006 and 2007, as well as received either tamoxifen or an aromatase inhibitor (anastrazole, letrozole, or exemestane) within 1 year of surgery. Nonadherence rates were calculated by race and low-income subsidy status for each year after the first prescription was filled through December 2011.

“Adherence to therapy is a critical factor in providing the best quality of care to patients,” said Greg A. Masters, MD, moderator of the briefing and chair of ASCO's Cancer Communication Committee. “Government programs, like Extra Help, can improve the care in underserved populations,” he said.

The researchers reported that 27% of the women were enrolled in the Extra Help program, which eliminated or reduced out-of-pocket (OOP) costs for hormone therapy. The OOP costs ranged from $155 to $428/year on average. A breakdown by race showed that 21% of white women, 70% of black women, and 57% of Hispanic women received the LIS.

In the first year of hormone therapy, overall adherence rates were similar for white women, black women, and Hispanic women, with rates of 64%, 63%, and 67%, respectively. Among women not enrolled in the Extra Help program, white women had significantly higher adherence rates at 62%, compared with black and Hispanic women (both at 55%).

Receiving the low-income subsidy also resulted in higher adherence rates across racial/ethnic groups, compared with those who did not receive the subsidy (71% vs 62% for white women, 67% vs 55% for black women, and 71% vs 55% for Hispanic women).

In addition, although hormone therapy adherence rates declined in years 2 and 3, adherence rate reductions were smaller among those who participated in the Extra Help program, and this trend was observed in all racial/ethnic groups.

“It's the LIS benefit that's contributing to a higher adherence rate for hormonal therapy,” said Biggers. “The Extra Help program holds promise in improving health equity and outcomes by reducing the disparity gap between different races and ethnicities,” she said.

Biggers A, Charlson J, Pezzin L, Laud P, Smith E, Smallwood A, et al. Medicare Part D Extra Help program and disparities in breast cancer treatment. Presented at ASCO's Quality Care Symposium. October 17-18, 2014.

Medicare Part D Subsidy Improves Outcomes, Reduces Racial Disparities in Women With Breast Cancer

Does Medicare coverage for patients with cancer match up to what they actually want covered? There appears to be a mismatch between covered benefits and beneficiary preferences that involves quality of life and financial burden of care, according to a study from Duke University. In the study involving 440 participants, 40 to 50% chose benefits that Medicare does not currently cover, namely, home-based long term care and concurrent palliative care. Participants were undergoing treatment for cancer, had recently been treated for cancer, or were helping to care for a patient with cancer enrolled in Medicare.

“Life span is key, but quality of life is key also,” said Donald H. Taylor Jr, PhD, an associate professor of public policy at the Sanford School of Public Policy at Duke University. “Patients are ready to have a more nuanced conversation” with their oncologists and hematologists, he said. He cautions, however, “not to over-interpret the results. This study is more like an agenda-setting commentary on policy.”

Medicare covers what it defines as “reasonable and necessary care” and its standards have guided what private insurers are willing to pay for as well, according to the authors in the study, published in the 

Participants were given a game board and provided with 50 stickers to allocate between 15 benefit categories, some of which were not covered by Medicare. They also met in small groups to go over educational materials about the Medicare benefit categories. The number of stickers given to each benefit category indicated the level of care the patient or caregiver wanted for that benefit.

Given the constraints—a variety of benefit options, a limited budget (the 50 stickers), and a chance to discuss the choices&mdash;around half were not very likely to devote all coverage to curative cancer treatment, said Taylor. These categories were for some level of unrestricted cash, home-based long term care services, or concurrent palliative care, which is beyond the current hospice benefits covered by Medicare.

“We have some evidence that demonstrates that for people who are directly facing death that they have some nuanced understandings of what benefit actually means,” he said.

Almost everyone allocated coverage to cancer itself, usually an intermediate or high level of care, and most also chose primary care and prescription drug coverage, which are covered by Medicare. More than 80% of participants also chose palliative care, home care, and nursing home care. Only 12% chose the maximum amount of cancer care.

The authors conclude that patients and care providers are signaling an interest in expanding benefits that focus on improving quality of life for those with cancer, even if resources are restrained. Although the study “didn’t actually impact patient’s care,” said Taylor, the findings suggest that “we just have to culturally learn how to talk about end-of-life decisions in a better way.”

	Taylor DH, Danis M, Zafar Y, et al. There is a mismatch between the Medicare benefit package and the preferences of patients with cancer and their caregivers. 

Does Medicare coverage for patients with cancer match up to what they actually want covered? 

Tony Berberabe, MPH