Posters presented at the National Comprehensive Cancer Network® (NCCN®) Annual Conference continue to grow in number and in quality. The ASCO Post presents a few that we found interesting at the recent 2019 meeting.
Next-Generation Sequencing Not Always Helpful in Practice
The value of next-generation sequencing tests is dependent on how it changes clinical management, if at all. Despite the prevalence of next-generation sequencing tests today, with few exceptions, there are often no clear recommendations as to when to order these assays, how to interpret the results, and whether a targeted intervention will be beneficial. Moreover, whether such a drug can be obtained and whether such treatment is financially justified may be unclear.
If I were the patient, I would no doubt still want this [next-generation sequencing] test to be ordered for me. We just need to be more realistic about what that means.— Christie Hancock, MD
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To shed some light on these questions as they arise in clinical practice, Christie Hancock, MD, and colleagues, of Advocate Lutheran General Hospital in Park Ridge, Illinois, reviewed the next-generation sequencing practices and outcomes at their community hospital. A review of 43 cases in which sequencing was obtained showed the most common tumor types for next-generation sequencing to be breast and colorectal.1 Results of sequencing changed management in 12 (28%) of the 43 patients. Two patients were able to enter a clinical trial, and the other 10 had therapeutic changes based on protein or mRNA overexpression.
For the 10 patients undergoing new treatment, this change in management did not translate into lasting responses, compared to patients without a change. Of the 43 patients, 40 died, at a median of 7 months from the time the test was ordered.
Dr. Hancock and her colleagues concluded that although next-generation sequencing yields a lot of information, it may be difficult to interpret in the clinical setting. It is also possible, they suggested, that the rare responses to new treatments were actually related more to tumor biology than to the interventions, Dr. Hancock told TheASCO Post. Her recommendation was for clinicians and patients to be aware of the limited clinical utility gained from ordering next-generation sequencing. But she added, “If I were the patient, I would no doubt still want this test to be ordered for me,” she added. “We just need to be more realistic about what that means.”
Cancers With Greatest ‘Burden’ Are Often the Least Funded
Despite substantial support for cancer research and advocacy in both the government and nonprofit sectors, the magnitude of funding is poorly correlated with the “burden” of individual cancers, according to Suneel Kamath, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago.2 “Disease-specific funding from the National Cancer Institute (NCI) and nonprofit organizations has little correlation with individual cancer burden,” he said.
Dr. Kamath and colleagues examined the GuideStar database to find all cancer nonprofit organizations with more than $5 million in annual revenue and identified funding from the NCI as well. They calculated total funding for each cancer type and looked at this in light of each cancer’s burden based on annual incidence, deaths, and person-years of life lost from Surveillance, Epidemiology, and End Results data. Altogether, they found 119 nonprofit organizations whose collective revenue was $6 billion and the NCI added nearly $3 billion. Half of the nonprofit organizations were “histology-agnostic,” and their funding accounted for $4.6 billion of the total. The rest of the funding was disproportionate to the burden of the disease, he reported at the NCCN meeting.
We saw that the number of new cases and deaths per year per tumor type has nothing to do with how much money goes toward the particular disease.— Suneel Kamath, MD
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“We found there is significant maldistribution of funding,” Dr. Kamath said. “We saw that the number of new cases and deaths per year per tumor type has nothing to do with how much money goes toward the particular disease. Breast cancer, for example, receives about $1 billion per year, whereas colorectal cancer is similar in incidence and has a high mortality rate, yet it receives $200 million. Though these two diseases are relatively similar in terms of new cases and deaths per year, there’s a huge gap in funding.” He said he was also struck by the disproportionate treatment of endometrial cancer, for which there are about 62,000 cases annually but funding of only $18 million.
By individual tumor type, cancers with the most combined NCI and nonprofit organization funding were breast cancer ($1 billion), leukemia ($448 million), lung cancer ($347 million), and prostate cancer ($303 million). The Pearson correlation coefficients between combined budget and incidence, mortality, and person-years of life lost were 0.74, 0.34, and 0.36, respectively, indicating poor correlation between a specific cancer’s burden on society and the magnitude of its funding. The analysis also revealed no nonprofits with revenue > $5 million devoted to esophageal, gastric, kidney, or bladder cancers.
“There is a significant need to increase awareness and support for many undersupported, but common and highly lethal cancers,” he said.
Cardiac Monitoring During Trastuzumab Treatment Needs Improvement
Per the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), for patients with breast cancer receiving trastuzumab, left-ventricular ejection fraction should be evaluated prior to and during treatment—every 3 months, according to the label approved by the U.S. Food and Drug Administration. Trastuzumab should be held for 4 to 8 weeks when ejection fraction decreases ≥ 16% from pretreatment values or falls below normal limits and decreases ≥ 10% from pretreatment values. For declines that persist > 8 weeks, or if the drug is stopped > 3 times for cardiomyopathy, trastuzumab should be permanently discontinued, according to the package insert.
Better documentation, easier accessibility to previous ejection fraction results, and a multidisciplinary team … will likely improve adherence to current recommendations for cardiac assessment [during trastuzumab therapy].— Heather Katz, DO, and colleagues
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Researchers from the Joan C. Edwards School of Medicine at Marshall University in Huntington, West Virginia, led by Heather Katz, DO, analyzed the charts of 59 patients with stages I to III HER2-positive breast cancer treated with trastuzumab between 2012 and 2017. They found compliance with these recommendations to be suboptimal.3
Left-ventricular ejection fraction was evaluated in all patients (100%) prior to treatment, every 3 months in 36 (61%), and at longer intervals in 23 (39%). Preserved ejection fraction was observed in 41 (69%) patients, whereas 18 (31%) had a decrease in left-ventricular ejection fraction by the defined criteria. Trastuzumab was not held appropriately in 4 of those patients (22%).
For 10 of 18 patients with declines in ejection fraction, this problem persisted, or they had stopped treatment > 3 times for cardiomyopathy. Trastuzumab was permanently discontinued appropriately in 4 (40%) of these 10 patients. The authors concluded that compliance with monitoring every 3 months was suboptimal, and clinicians also need to better recognize when to hold trastuzumab to prevent cardiotoxicity.
“Better documentation, easier accessibility to previous ejection fraction results, and a multidisciplinary team (breast navigator, cardiologist, oncologist, and pharmacist) will likely improve adherence to current recommendations for cardiac assessment,” the authors suggested in their poster.
Registry of 7,000 Patients Proves Efficacy of Scalp Cooling
Worldwide, scalp cooling is being introduced to prevent chemotherapy-induced alopecia. In the Netherlands, this service has been offered in many hospitals since 2005, whereas in the United States, approval was obtained in 2015 for breast cancer and in 2017 for all solid tumors.
At the NCCN meeting, Dutch investigators reported data from a prospective registry of 7,378 patients collected between 2006 and 2017; it included patients of any age or gender, with any type and stage of solid tumors, who received chemotherapy associated with potentially severe hair loss and used scalp cooling.4 Most (75%) had breast cancer, and 8% had prostate cancer. In general, the preinfusion cooling time was 20 to 30 minutes, and postinfusion cooling time was 90 minutes. The primary outcome was the percentage of patients not wearing a wig or head cover (patient-reported).
Corina van den Hurk, PhD
Scalp cooling successfully reduced hair loss in most patients, said Corina van den Hurk, PhD, of the Netherlands Comprehensive Cancer Organisation in Utrecht. Its efficacy was largely related to the chemotherapy regimen, varying from > 80% for taxane monotherapy to < 10% for the combination of docetaxel, doxorubicin, and cyclophosphamide. The study also found that patients’ opinions about the nursing expertise with scalp cooling varied considerably among hospitals, with positive opinions ranging from 35% to 75%.
DISCLOSURE: Drs. Hancock, Kamath, and Katz reported no conflicts of interest. Dr. van den Hurk has received a grant for an international scalp cooling registry from Dignitana and Paxman as well as travel expenses from Paxman.
1. Hancock C, Kelby S, Krupa K, et al: The clinical outcomes of NGS testing in the community. 2019 NCCN Annual Conference. Abstract CLO19-034. Presented March 21, 2019.
2. Kamath SD, Kircher SM, Benson AB: A comparison of cancer burden and funding from the National Cancer Institute and nonprofit organizations reveals disparities in the distribution of funding across cancer types. 2019 NCCN Annual Conference. Abstract HSR19-094. Presented March 21, 2019.
3. Katz H, Jafri H, Leigh EC, et al: Trastuzumab induced cardiotoxicity: Are we monitoring and managing appropriately? 2019 NCCN Annual Conference. Abstract QIM19-132. Presented March 21, 2019.
4. Van den Hurk, Dercksen W, Vriens B, et al: CLO19-056: Scalp cooling proved to be successful in the prevention of alopecia in >7,000 patients with solid tumors. 2019 NCCN Annual Conference. Abstract CLO19-056. Presented March 21, 2019.