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Tuesday, June 30, 2015

 

BY MARK L. FUERST

 

SAN FRANCISCO--A new gene expression profile (GEP) test more accurately predicts the risk of metastasis and survival in patients with cutaneous melanoma compared with the standard predictive method currently used to guide patient management, researchers reported here at the American Academy of Dermatology Annual Meeting. With more testing, they and other experts said, it may allow oncologists to know which patients need early treatment to prevent disease progression.

 

“There is great variability in prognosis in stage 2 melanoma patients, and these patients benefit from increased surveillance or better treatment of early metastatic disease. The value of the GEP test to an oncologist is to know which patients to worry about, and to treat these patients more carefully,” the lead author, Laura Ferris, MD, PhD, Director of Clinical Trials in the Department of Dermatology and Associate Professor of Dermatology at the University of Pittsburgh, said in an interview.

 

“The ability to accurately predict the risk of metastasis and death among patients with cutaneous melanoma is of the utmost importance in guiding clinical decision making. Together with the previously published data, our study shows that the GEP test can help to identify high-risk patients."

 

She presented the results of a study that showed that the noninvasive, 31-gene GEP test, DecisionDx-Melanoma, performed significantly better than the American Joint Committee on Cancer (AJCC) Individualized Melanoma Patient Outcome Prediction Tool in predicting five-year distant metastasis-free and overall survival.

 

The GEP test stratifies patients into low (class 1) or high (class 2) risk, and provides a linear probability score from 0 to 1 associated with the similarity of the biological signature to an established and clinically useful training set.

 

She and her co-researchers examined the records from 355 node-negative melanoma patients who met AJCC criteria. As a means of comparing the GEP and AJCC tests, five-year survival rate cutoff scores of 79 percent and 68 percent were used. The cutoffs reflect five-year survival rates for Stages IIA or IIB melanoma patients, which can result in significantly different treatment strategies, according to National Comprehensive Cancer Network guidelines.

 

“The GEP test predicted melanoma risk more accurately than, and independent of, the AJCC online prediction tool,” Ferris said, noting that 15 patients who were predicted to be low risk in AJCC were class 2, and died of melanoma. Only two patients predicted to be class 1 in the GEP test were high risk in AJCC.

 

“Most patients who are high risk in the AJCC criteria are likely to be class 2 with the GEP test, and those who are low risk in the AJCC criteria are likely to be class 1 in the GEP test,” she said. “The GEP test is more likely to predict metastatic melanoma within five years.”

 

Patients had slightly more than twice the risk of distant metastases-free survival if they had a high-risk GEP score compared with a high-risk AJCC score. For overall survival, patients were 1.5 times more likely to have a poor outcome if they had a high-risk GEP than a high-risk AJCC score.

 

Asked for his opinion, though, Klaus J. Busam, MD, Director of both the Dermatopathology Service and the Dermatopathology Fellowship Program of Memorial Sloan Kettering Cancer Center, cautioned: “The GEP has not yet been adequately tested for outcomes prediction. I welcome efforts to improve prognostication, and it is a very good start, but we have only a few hundred cases of the GEP test. The AJCC has 60,000 cases. We need good prospective studies of the GEP test.”

 

The study’s first author, Pedram Gerami, MD, Associate Professor in Dermatology, Pathology, and Pediatrics-Dermatology at Northwestern University Feinberg School of Medicine, echoed his coauthor:  “The GEP test is an independent predictor of metastasis for stage 1 or 2 melanoma and is a stronger predictor of metastatic recurrence than AJCC stage.”

 

Second Validation Study

In a separate session at the meeting, Gerami presented the results of a second validation study of the GEP test to predict the metastatic risk associated with cutaneous melanoma. (A first validation study had found that the GEP test was an objective tool that accurately predicted metastatic risk in sentinel lymph node (SLN) biopsy-eligible patients in a multicenter cohort of 217 melanoma patients, and found a five-year disease-free survival rate of 97 percent for GEP class 1 patients versus 31 percent for GEP class 2 patients.)

 

The second validation study found that for every category, there was a bigger separation of class 1 versus class 2 compared with SLN biopsy positive or negative patients, he said. The negative predictive value was higher with the GEP test (79%) than with SLN biopsy (56%).

 

“If I tell a melanoma patient that he is GEP class 1, that’s more reassuring than telling him he has a negative SLN biopsy. For GEP class 2 patients it does not matter if the SLN is positive or negative. The overall survival rate is about the same,” Gerami said.

 

About one-third of the patients were GEP class 1 and had a negative SLN biopsy; they had an overall five-year disease-free survival rate of 83 percent. In a small cohort of patients who had a GEP class 1 and positive SLN biopsy, the overall five-year disease-free survival rate was 53 percent.

 

Gerami admits more studies are needed to verify the results of the GEP test, which has been available for more than a year. “The main indication for the GEP test is to identify node-negative patients who may have other tumor characteristics that are worrisome for high-risk disease. A huge proportion of patients who die from melanoma are SLN biopsy negative. We have a lot of preventive therapies available. We can inform patients who are class 1 on the GEP test that it is likely they do not have metastatic disease, and for GEP class 2 patients, we can increase their imagining schedules. Why not consider adjuvant therapy for stage 2 patients even if we do not find melanoma?”

 

‘Use in Combination with SLNB’

Based on data from this study and the prior validation study, Gerami said he and his colleagues propose that the GEP test be used in combination with SLN biopsy to help clinicians further stratify patients as higher- versus lower-risk. The combined use of these two prognostic tests may identify more than 80 percent of patients who are at risk for metastasis compared with SLN status alone, providing a significant opportunity for improved patient treatment, he said.

 

Still, Busam expressed concerns: “The biggest problem I have with the rollout is the proposed value of the GEP test--that is, to pick up patients who will benefit from SNL biopsy. SLN biopsy is a surgical prognostic test. If we want a good prognostic test, it should help us avoid SLN biopsy. If the company trusts class 1 results so much, then the class 1 patient does not need SLN biopsy. If it is better than SLN biopsy, why use the test to recruit patients to have surgery to give a test result that is inferior to the one you propose? I’m having trouble designating clinical value to the test.

 

“I’m all for using any means to improve tumor prognostication to avoid the need for surgery, but it is not therapeutic and does not help survival,” he continued. “The GEP test has prognostic value, mostly if a patient participates in a clinical trial. For personal life planning and treatment purposes, I wish it was robust enough to avoid SLN biopsy. If we want to upstage patients and have more scans--say, five times a year instead of once a year--what are the scans really doing? They are not saving lives. I caution against using the test if a patient is class 2. The patient may become depressed and have unnecessary tests for years to come that may not be beneficial.

 

“We already have ways to improve prognostication. We can add in clinical information, get tumor-infiltrating lymphocyte levels, and mutational status of NRAS and BRAF, which are targets that can be treated. The GEP test should also be measured against less expensive parameters that are known to make prognostication of a primary tumor more accurate. Don’t forget the power of visual recognition. The microscope is still a great tool.”

 

Also asked for his opinion, John Votto, MD, Professor of Surgery at Oregon Health & Science University, generally agreed: “We need a test about how and when a patient will fail. Can we specify a gene profile for a pattern of failure? We need to use genetics to determine when a patient should have SLN biopsy or go straight to systemic therapy, or have both. These data are early and exciting, but are only on a few hundred patients. We need confirmation in a prospective trial.” 

 

Next Step

The next step, Ferris said, is to use the GEP test in the treatment of patients with high-risk, stage 2 melanoma. “Most patients in our cohort had stage 2 melanoma and were GEP class 2. Some patients with stage 2 melanoma do well, showing improved survival with targeted therapies.”

 

There are more false positives with the GEP test than with SLN biopsy. “We speculate that when we find early melanoma, some lesions are thinner, less aggressive tumors and others are thicker, more aggressive ones. There is a window of cure. I predict the GEP test has the potential to catch melanomas in the window of cure before they metastasize,” she said.

 

Outside of the research setting, Ferris said she has used the GEP test on 10 melanoma patients who have thinner, 0.5-1 mm lesions. The patients she has selected for the GEP test “have an increased mitotic rate and evidence of ulceration, and are questionable candidates for SLN biopsy. Others are patients who want SLN biopsy, but do not meet the criteria. The GEP test can assure these patients they do not need an additional procedure. If patients have very deep, four to five millimeter lesions, the GEP test is unlikely to be necessary since we know that these are high-risk patients.

 

“There is no good consensus on how to deal with intermediate-risk melanoma,” she continued. “We need a consensus statement on how the GEP test fits in. I believe it is predictive.  Most SLN biopsies are negative. If a patient is class 1, the chance of a negative SLN biopsy is low. Then we would only do SLN biopsies on class 2 patients. This is reasonable, but requires the entire melanoma community to come together. This would save a lot of procedures and money.”

 

Cost is also a factor, she noted: A sentinel lymph node biopsy costs $12,000 to $15,000 versus $3,000 to $7000 for the GEP test. Some insurance companies pay a reimbursement rate of $1,500 for the GEP test, and if insurance does not cover the test, the developer, Castle Biosciences, told OT that it will not go to the patient for payment.


Monday, June 29, 2015

 

 

BY SARAH DIGIULIO

 

The Oncology Nursing Society has issued a position statement on the roles and requirements of the oncology nurse navigator (ONN). The statement also notes the qualifications necessary to meet those requirements, which includes certification through a National Commission for Certifying Agencies-accredited organization.

 

“Patients and families benefit from the care coordination efforts of an ONN,” ONS President Margaret Barton-Burke, PhD, RN, FAAN, said in a news release. “Our goal is to support and promote the role and qualifications of the ONN in the delivery of evidence-based, cost-effective, and quality patient-centered care.”

 

Because of the complexity of cancer treatment today, understanding the diagnosis, treatment, and health care system requires the complex skill of an oncology nurse navigator—and navigation includes the entire health care continuum, from prevention to screening to diagnosis to treatment to survivorship to end-of-life, the statement notes.

 

The Impetus

Impetus for the statement came from ONS’s Nurse Navigator Special Interest Group, who was responding to queries from the ONS membership and the public about the Society’s perspective on nurse navigators’ roles, according to a member of the ONS Public Relations Department. The Nurse Navigator Special Interest Group worked with members of the ONS Board of Directors to draft final version.

 

Jean Sellers, RN, MSN, ONS’s Nurse Navigator Special Interest Group coordinator, added in a news release: “ONNs greatly contribute to nursing research that supports the understanding of nurse-sensitive, patient-specific outcomes resulting from oncology nurse navigation.”

 

Limitations in published research and the inability to replicate navigation programs and processes often relate to the absence of standardized navigation roles, job descriptions, processes, and oncology nurse navigator qualifications, the statement notes.

 

And according to the statement: “As cancer care evolves, so does the ONN role to meet the needs of patients, families, caregivers, and survivors while serving the needs of the cancer care delivery systems providing evidence-based, cost-effective, and quality patient-centered care. To this end, ONS acknowledges the imperative need to address the ONN role.”

 

Positions Outlined

Additionally, the following positions of ONS are outlined in the statement:

  • Nurses in oncology nurse navigator roles should possess certification through one of the National Commission for Certifying Agencies-accredited certifications offered by the Oncology Nursing Certification Corporation—minimally, Oncology Certified Nurse (OCN);
  • Additional research is needed to systematically characterize and compare navigator activities within and across clinical programs;
  • Oncology nurse navigators contribute to or conduct nursing research that supports the understanding of nurse-sensitive, patient-specific outcomes resulting from oncology nurse navigation;
  • A core competency of oncology nurse navigators includes care coordination;
  • Oncology nurse navigator services begin with prevention and screening activities and continue through diagnosis, treatment, survivorship, and end-of-life care;
  • Oncology nurse navigators advocate for quality, cost-effective, patient-centered outcomes, and facilitate communication between the patient/survivor, caregiver, and interprofessional cancer care team; and
  • When available, oncology nurse navigators are responsible for overseeing patient navigation processes, in conjunction with the multidisciplinary team, while including integration of nonprofessionals or lay patient navigators.

The full statement is published on the ONS website and will be published in a future 2015 issue of the Oncology Nursing Forum.


Monday, June 29, 2015

 

BY MARK L. FUERST

 

NEW YORK--An update to the Fourth Edition of the World Health Organization (WHO) Classification of Hematopoietic and Lymphoid tissues is in progress. Nancy Lee Harris, MD, Professor of Pathology at Massachusetts General Hospital and Harvard Medical School, discussed the changes here at the Modern Radiation for Lymphoma: Updated Role and New Rules” meeting at Memorial Sloan Kettering Cancer Center.

 

“The fourth edition is now six years old, but WHO will not begin work on a fifth edition until all volumes of the fourth edition are published,” she said. “WHO has now agreed to an update,” which is expected to be available in about a year.

 

Harris noted that multiple meetings of the editors were held between 2012 and 2014, with senior advisors added in genetics and myeloid diseases. Clinical Advisory Committees (Lymphoid and Myeloid) met in March 2014. “No one gets everything he or she wants in this collaborative effort, but we do try to arrive at a consensus that benefits our patients.”

 

In an interview, elaborating on remarks he made at the meeting, Saul Rosenberg, MD, Professor of Medicine and Radiation Oncology Emeritus at Stanford University School of Medicine, said, “WHO classification is based on good science and ideas, but the new update is very complicated and extremely complex. It may overestimate the clinician’s ability to handle it. We only have a limited number of treatments that work. I worry that every patient will be given a different diagnosis.”

 

Harris responded: “In the 1990s, when we published the REAL [Revised European American Lymphoma] classification, we were advised by clinicians to simplify the classification for community oncologists. At a CME meeting where this was being discussed, one of the participants said to me during a break, ‘I’m a community oncologist, and I get this! You don’t have to simplify it for me!’ I believe that when we identify distinct diseases, with distinctive pathological and clinical features, it is easier both for pathologists to make a diagnosis and for clinicians to understand what their patients have and to individualize treatment. Precision medicine requires precise diagnoses.”

 

She added: “We are not inventing new diseases, we are discovering new diseases. It is no different from astronomy or genetics or microbiology. You do not hear people complaining when a new planet or gene or microbe is discovered.”

 

Harris noted that after the exchange of views between herself and Rosenberg at the meeting, a radiation oncologist approached her at lunch and said, “I think I recognized a patient of mine in one of the new entities you described. It was a young man in his early 20s who presented with a large neck mass. It was completely resected, and the pathologist called it ‘follicular lymphoma grade 3B with diffuse large B-cell lymphoma.’ The patient had no other sites of disease, but had no insurance and couldn’t afford further treatment. One year later, he returned with upper airway obstruction and had a large mass of the ipsilateral tonsil, which was recurrent lymphoma. At this time he had insurance, so he was treated with chemotherapy and it resolved.

 

“We are considering local radiation, but the medical oncologist says that because it is follicular lymphoma, he is recommending maintenance rituximab. If this is the new entity you described, diffuse large B-cell lymphoma and follicular lymphoma grade 3B with IRF4 rearrangements, it sounds like this has nothing to do with conventional follicular lymphoma, and the patient should have a good outcome without maintenance rituximab.” The radiation oncologist was absolutely right, Harris said.

 

A Brief History of Lymphoma Classification

In the 1970s, there were multiple lymphoma classifications in use, Harris related. “An international study, led by exasperated clinicians, failed to result in a consensus on the ‘best’ classification, and led to the development of the Working Formulation, which was designed to translate between classifications. It included broad prognostic groups based on the survival of patients in the study, and these groups became more important than specific pathological categories, which were designed to be broad and heterogeneous, so that all entities in all classifications could be covered.”

 

In the 1980s to the 1990s, the problem of classification persisted. The Working Formulation became the major American classification, but the Kiel Classification was used in Europe, and some in the U.S. used the Lukes and Collins classification. In addition, new entities were recognized and new immunophenotypic or genetic features were discovered for some recognized entities, but there was still no consensus among pathologists or clinicians on the definitions of entities or criteria for diagnosis.

 

In 1994, the International Lymphoma Study Group published the REAL classification, which was a consensus list of lymphoid neoplasms that could be recognized by pathologists and that were clinically distinctive, Harris continued. This also included input from a meeting with clinicians. In 1997, an international clinical study of the REAL classification found that it identified reproducible categories that covered more than 95 percent of lymphomas, and  that were clinically relevant, not only in terms of prognosis, but with distinctive epidemiology and clinical presentations.

 

In 2001, in the Third Edition of its series of books on classification of tumors, the World Health Organization published the WHO Classification of Tumours of the Hematopoietic and Lymphoid Tissues. “The development of this classification provided us the opportunity to develop a broader consensus on lymphoid neoplasms and to apply the principles of the REAL classification to myeloid and histiocytic neoplasms,” Harris explained. “These classifications, like the REAL classification, continued to have clinical advisory committees and consensus meetings of pathologists, with more than 200 international pathologists and clinicians participating.”

 

The 2001 WHO classification represented the first international consensus on classification of hematologic malignancies, and in 2008, the 4th Edition was published.

 

REAL/WHO Classification Principles

The REAL/WHO Classification Principles are to define distinct disease entities that can be recognized by pathologists and that have clinical relevance, she said. A constellation of features (morphologic, immunophenotypic, genetic, and clinical) define each disease entity. The relative importance of each feature varies among diseases.

 

“Since we do not know the underlying cause of most lymphomas, the relative importance of each feature varies among diseases. There is no ‘gold standard,’” she said. Diseases are stratified according to postulated normal counterpart and stage of differentiation to the extent possible, and sorted according to clinical and morphologic similarities.

 

The 2008 Fourth Edition classification, compared with the 2001 Third edition, recognized more diseases, 108 in all, including 50 myeloid and acute leukemias, 53 mature B-cell lymphomas, T-cell lymphomas, and Hodgkin lymphomas, and five histiocytic lymphomas. “Many are defined by genetic and immunophenotypic features, as well as morphology. Correct classification is required to determine appropriate treatment,” Harris said.

 

Importantly, a number of subtypes of diffuse large B-cell lymphomas (DLBCL) are included in the Fourth Edition:  

  • DLBCL not otherwise specified;
  • DLBCL associated with chronic inflammation;
  • Lymphomatoid granulomatosis;
  • Primary mediastinal (thymic) large B-cell lymphoma;
  • Intravascular large B-cell lymphoma; ALK-positive DLBCL;
  • Plasmablastic lymphoma;
  • Primary effusion lymphoma; and
  • Large B-cell lymphoma arising in HHV8-associated multicentric Castleman Disease.

The WHO 4th Edition includes an equally long list of mature T-cell and natural killer-cell neoplasms.

 

Regarding the details of what is new in the WHO update, Harris said that many of the changes are still under discussion, a final consensus has not been reached on some issues, and the actual writing is just beginning.

 

 


Saturday, June 27, 2015

BY KURT SAMSON

 

Childhood survivors treated with high doses of anthracyclines, high doses of chest radiation, or a combination of both, should undergo lifelong surveillance for cardiomyopathy. That is the conclusion of a large-scale review of the medical literature by an international group that attempted to coordinate existing recommendations and understand what had been differing conclusions.

 

The study (Lancet Oncol 2015;16:e123-e136), by the International Late Effects of Childhood Cancer Guideline Harmonization Group, also advised that children treated with moderate or low doses should be considered for surveillance depending on other cardiac risk factors.

 

“We have seen tremendous advances in childhood cancer treatment, with more than 80 percent of children expected to be survivors for at least five years, but childhood cancer survivors, regardless of their current age, should be aware of their increased risk of cardiovascular problems,” said the chair of the consortium’s cardiomyopathy working group, Saro Armenian, DO, Director of the Childhood Cancer Survivorship Clinic at City of Hope. “This is a lifelong risk, and many of these problems don’t appear until 10 or 20 years after treatment, so surveillance and monitoring should continue throughout their life.”

 

According to American Cancer Society estimates, there are more than 400,000 childhood survivors in the United States, and the number is expected to reach half a million by 2020.

 

Echocardiography

The panel recommended echocardiography as the primary method of surveillance, although other forms of screening, such as magnetic resonance imaging, should also be considered. Screening is advised starting two years after the completion of therapy and should be repeated every five years, although more frequent testing is reasonable for those at higher risk.

 

As they described in the study, the authors conducted a comprehensive review of all available literature to assess risk and make recommendations on how best to protect the hearts of childhood cancer survivors. Even with all the treatment advances, more than 40 percent of childhood cancer survivors who are still alive 30 years after their diagnosis have a severe or life-threatening chronic health disorder, including heart disease.

 

Cardiovascular complications--coronary artery disease, stroke, and congestive heart failure--have emerged as a leading cause of illness or death in survivors. The investigators also said that childhood cancer survivors should be especially careful to manage their risk of high blood pressure and diabetes, both of which raise the likelihood of heart disease.

 

Armenian noted that some of this is uncharted territory, since survivors of childhood cancer reaching their 50s and 60s is a fairly new phenomenon. But if they are screened early, even if asymptomatic, there is a chance to mitigate the problems.

 

The study showed that survivors have 10 times the risk for atherosclerosis, 5.9 times the risk of congestive heart failure, 6.3 times the risk of pericardial disease, and 4.8 times of the risk for heart valve disease. The risks were especially high for those treated with anthracycline drugs, such as doxorubicin, or high-dose radiation therapy to the heart.

 

“We are trying to develop uniform guidelines. Health care groups around the world have recommended different screening parameters and definitions for these children, and there is some discordance, which can result in confusion,” he said. “We found compelling evidence that the use of anthracyclines and chest radiation can raise the risk of later cardiovascular issues in long-term survivors, and that this requires regular monitoring.”

 

While there has been increased uniformity in monitoring and screening in the United States and Europe, many other countries lack guidelines. This is especially true for certain subsets of survivors who might have other cardiovascular risk factors.

 

“As we get more information, we will continue to update these guidelines,” Armenian said. “It is important to emphasize that this has been an exhaustive effort as well as a transparent process of evaluation. We relied on only high-impact, high-quality research.”

 

Nonetheless, he said that there is a relative lack of research on such survivors and long-term heart issues. When only little evidence was available, the researchers extrapolated data from other populations at risk of congestive heart failure. “Importantly, there are key gaps in our knowledge of the frequency of screening in different risk groups, the role of cardiac MRI, myocardial strain testing, three-dimensional echocardiography, and the use of cardiac blood biomarkers in primary surveillance.

 

“More research is also needed in the prognostic value of changes in intermediate echocardiographic indices of left ventricular systolic and diastolic function as well as the efficacy of early intervention strategies for congestive heart failure prevention.” Answers to these and other key questions can be addressed only through a comprehensive and systematic approach requiring multidisciplinary and international collaborations in order to access large patient populations, he noted.

 

Harmonization Important

Asked for her perspective, Kirsten K. Ness, PT, PhD, Associate Member in the Departments of Epidemiology and Cancer Control NS Pediatric Medicine at St. Jude Children's Research Hospital, said the effort at harmonization by the researchers at many medical facilities across the globe is impressive.

 

“This paper provides a solid reason that such harmonization is necessary. It emphasizes that there is no safe length of time after childhood cancer after treatment with anthracyclines or radiotherapy that such patients should not be monitored for cardiovascular problems.”

 

In a 2011 study published in Pediatric Blood Cancer (2011;57:467-472), she and her colleagues evaluated the effectiveness of surveillance echocardiograms given according to the Children's Oncology Group's long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers after one year of treatment--notably the frequency of abnormal echocardiograms. A total of 16.8 percent of survivors had abnormal echocardiograms at a median of 2.9 years, and treatment with an anthracycline dose higher than 300 mg/m2 and radiation to a field involving the heart predicted an increased risk of an abnormal echocardiogram. However, even survivors in the lower risk groups showed abnormalities up to four years after treatment.

 

The researchers concluded that periodic echocardiographic surveillance of childhood cancer survivors can uncover abnormalities that can appear even one year after treatment that require further evaluation. Moreover, cardiac issues can occur even in survivors considered to be at low risk.

 

“I think that oncologists and especially cardio-oncologists are aware of the risk, especially if patients are seen at survivorship clinics. But among the general public this is not the case, and young adult survivors may not have an understanding of the risk unless they get a care plan. Further, general pediatricians and general practitioners need greater awareness.”

 

Regarding lifestyle factors that can predispose individuals to cardiac problems such as smoking, hypertension, physical inactivity, and diabetes, Ness said that this presents an opportunity for survivors: “I think most of them receive counseling about lifestyle factors. This is important because survivors have some control over these factors and it can be an opportunity for them to improve their long-term survival.”

                                             

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Started in 2010

The International Late Effects of Childhood Cancer Guideline Harmonization Group, started in 2010, is a worldwide effort by several national guideline groups and the Cochrane Childhood Cancer Group, in partnership with the PanCare Childhood and Adolescent Cancer Survivor Care and Follow-up Studies consortium of 16 European institutions to collaborate on developing guidelines.


Friday, June 26, 2015

 

BY HEATHER LINDSEY

 

More than a third of counties in the United States are located more than 50 miles from the nearest gynecologic oncologist, which adds up to nearly 15 million women with reduced access to care for ovarian and other gynecologic cancers, according to new research.

 

The study, published in the July issue of Gynecologic Oncology (2015;138;115-120), is the first national, spatial analysis to identify specific areas in the U.S. where women may be at an increased risk for poor clinical outcomes.

 

The study’s lead author, David Shalowitz, MD, a gynecologic oncology fellow at Perelman School of Medicine at the University of Pennsylvania, noted that although there has been a great deal of research evaluating social and demographic correlates as barriers to health access overall, the geographic component has been understudied, especially in gynecologic cancers.

 

The takeaway message from the study is that “where you live matters,” commented Kunle Odunsi, MD, PhD, Deputy Director of Roswell Park Cancer Institute and Chair of the Department of Gynecologic Oncology. “If you live close to a high-volume cancer center, you’re likely to get referred there. That increases the likelihood of getting appropriate, best practice care. Living in other certain geographic areas decreases this likelihood.”

 

Also commenting, Camille Gunderson, MD, a gynecologic oncology fellow at the University of Oklahoma Health Sciences Center Stephenson Cancer Center, said that previous research has shown that gynecologic cancer patients cared for by physicians other than gyn oncologists have inferior outcomes, including shorter survival, and that while such outcomes are not addressed within this manuscript, they would presumably be present in low-access counties.

 

Study Details

Using spatial analysis software, called ArcGIS, as well as professional directories and census records, the authors determined how many gynecologic oncologists were located within 50, 100, and 150 miles of county borders for 3,143 counties in the United States.

 

A total of 36 percent of the counties were located more than 50 miles from the closest gynecologic oncologist, affecting 14.8 million women (9.8% of the population). Additionally, 2.7 and 1.1 percent of women were located even further away—at least 100 and 150 miles away, respectively.

 

Overall, 47 states had at least one county located more than 50 miles from the nearest gynecologic oncologist, and most of these low-access counties were in the Mountain-West and Midwest. All states except North Dakota and Wyoming contained a primary professional address for at least one gynecologic oncologist; all of North Dakota is located more than 50 miles from the nearest primary address of these providers. The counties with the greatest number of gynecologic oncologists within 50 miles were located near major metropolitan areas, primarily along the Atlantic coast between Atlanta and Boston, the researchers found.

 

Based on available county and national data, the researchers estimated, an annual incidence of the following cancers in low-access counties:

  • 1,772 ovarian cancers (8.5% of all cases nationally);
  • 4,754 uterine cancers (9.9%); and
  • 1,137 cervical cancers (9.3%).

The investigators found that residents of lower-access counties had a lower median household income and were more likely to be white or Hispanic and less likely to be black. “We know that black women do face significant disparities in access to gynecologic oncology care, but our findings suggest that the source of this is likely not related to distance to the closest gynecologic oncologist,” Shalowitz said.

 

He and his coauthors--Alexandra M. Vinograd, MD; and Robert L. Giuntoli II, MD--analyzed hospital referral regions (HRRs), developed by the Dartmouth Atlas of Healthcare, and concluded that 23.5 million women (15%) may also experience barriers to care based on their referral network. Although HRRs were developed for neurosurgical and cardiovascular procedures, they can also be used as a surrogate for gynecologic oncology referral patterns, Shalowitz said. “The distance to an oncologist is not the whole story. Women are likely to go to where they are referred, and we wanted to know which regions of the country had barriers to care, based on referral networks.”

 

The study showed that 123 of 306 referral networks (40%) nationally do not have access to a gynecologic oncologist, suggesting that women would have to travel outside of their referral network to connect with a specialist. Based on the researchers’ estimates, 7,663 women with gynecologic cancers per year likely experience distance-related barriers to accessing appropriate care from a specialist.

 

Benefits of Spatial Analysis

Gunderson praised the methodology, pointing especially to the “unique software”—“Spatial analysis is different from just computing the distance between zip codes, which is what has been done in the past. The results are probably more applicable than when people report travel time or distances,” she said, adding that she hopes to see more of this type of analysis for population-based access-to-care studies.

 

State level analyses are limited by boundaries, Shalowitz explained. “So if someone lives near a state border, she may be a great distance to the nearest gynecologic oncologist within that state. But, it may not be so burdensome to cross state lines. This national spatial analysis was designed to address this limitation of state-level studies.”

 

In Line with Previous Research

Overall, a patchwork of prior data suggests that geographic access to care may be a nationwide problem, he continued.

 

He and his colleagues knew from earlier research (Bristow et al: Gynecol Oncol 2014;132:403-410) that there are areas in various states that were far away from a gynecological oncologist. “We have a reason to believe that women who are greater than 50 miles from a gynecologic oncologist do have a higher likelihood of receiving care from a low-volume hospital or a center that doesn’t adhere to guidelines, which has been associated with a six percent reduction in five-year survival for individuals with ovarian cancer,” he said.

 

Additionally, at the national level, research demonstrates that a quarter to half of women with ovarian cancer receive care at a low-volume center or do not receive care adherent to National Comprehensive Cancer Network guidelines (Cliby et al: Gynecol Oncol 2015;136:11-17). In an email to OT, William A. Cliby, MD, a gynecologic oncologist at Mayo Clinic, wrote that this research is important because center volume was linked to both delivery guideline care and survival.

 

Overcoming Barriers

Odunsi said that physicians, including those in low-access counties, of course want the best outcomes for their patients, but the question is how to overcome geographic barriers. “One option is to place more specialists in low-access areas, but this may be challenging, partly because of the time it may take. Patients are sick now and need appropriate care.”

 

Having a gynecologic oncologist available or the type of tertiary care center that can deliver complex care, particularly initial surgery and treatment planning, may be unrealistic in low-density populated areas, Cliby noted.

 

Another solution, he continued, may be for payors and providers to develop mechanisms to get patients to regional centers of excellence, particularly in low-density regions, and to improve delivery of complex care at high-volume and expert centers. Travel costs and local lodging are important components of helping patients.

 

In addition, physicians need to educate patients about the differences between the conveniences of being treated locally versus traveling to receive evidence-based care, Odunsi said.

 

Expanding current outreach sites to low-access counties could help with providing care, Gunderson said. “If the distance is too great, we can bring the gynecologic oncologist closer to patients to help to bridge the gap.”

 

However, outreach programs can be inefficient and may not include care from the larger tertiary facility that is often needed, Cliby pointed out. Telemedicine may thus help provide consultations to more patients.

 

Shalowitz said that the research team was able to create detailed maps of low-access counties that could suggest where gynecologic oncologists should focus on outreach to ensure women have equal access to standard of care. However, before more focused interventions are developed, researchers need to see whether and how low-access counties correlate to gynecologic oncology health outcomes.