An estimated doubling of the number of people over age 65 over the next two decades and simultaneous increases in cancer incidence, prevalence, and survivorship are expected to create a situation where the number of cancer patients far outstrips the number of oncologists available to treat them, according to a new report released last week.

Developed for the American Society of Clinical Oncology (ASCO) by the Association of American Medical Colleges (AAMC), the report estimates that by 2020 visits to oncologists will increase by 48 percent, while the projected supply of oncologists is expected to grow by only 14 percent over the same time period. The result: A shortfall of 9.4 to 15.1 million visits annually.

“We think this is a very serious situation that deserves a response sooner rather than later,” said study co-author Dr. Edward Salsberg, director of the AAMC Center for Workforce Studies.

“The whole force of the medical care delivery system is going to really be challenged 10, 15 years from now to meet what we see is a greatly increased demand [for oncology services],” added Dr. Michael Goldstein, a study co-author from Beth Israel Deaconess Medical Center in Boston and chair of the ASCO Task Force on the Oncology Workforce.

To develop its work force supply estimates, AAMC used new and existing surveys of current oncology fellows, directors of oncology fellowship programs, and 4,000 practicing oncologists from across the country. The demand component of the study relied on incidence and prevalence estimates and oncologist visit rates developed by NCI staff from the Health Services and Economics Branch and the Statistical Research and Applications Branch in the Division of Cancer Control and Population Sciences (DCCPS), using data from the Surveillance, Epidemiology and End Results (SEER) program and the SEER-Medicare Linked Database (see the Director’s Update for more details).

A number of specialty physician organizations and other groups have released similar forecasts over the past few years, including projections of shortfalls in cardiology, critical/emergency care, and primary care.

For specialties like cardiology and oncology, the “graying” population is particularly concerning, because both heart disease and cancer are closely associated with older age. In addition, the available data suggest the physician pipeline isn’t robust enough to satisfy future demand. For example, according to a study published last year in Academic Medicine, the number of physicians retiring annually will swell from 9,000 in 2000 to more than 22,000 by 2020, with no expected corresponding growth in medical school graduates. And, Dr. Goldstein explained, based on the survey responses from oncology fellowship program directors, funding issues will limit any increase in the number of oncology fellowship slots to an estimated 8 percent by 2010-11.

In the ASCO/AAMC study, the baseline supply/demand analysis was performed assuming that current physician practices (number of patient visits, use of physician assistants and nurse practitioners) and care delivery patterns would remain the same. However, different scenarios were modeled to account for potential changes that could affect both supply and demand, including greater use of electronic medical records (EMRs), delaying retirement of existing physicians, and greater reliance on primary care physicians during certain care periods.

Some changes made the work force shortfall less severe, particularly expanded use of EMRs and creating more oncology fellowship positions. But no single measure or combination was a panacea, and there were also factors that could exacerbate the shortfall.

“The bottom line is that no matter which scenario we looked at, it is likely the shortage will continue,” Dr. Salsberg said.

ASCO has assembled an implementation group with expertise in clinical practice, cancer education, research, and oncology training to develop recommendations to address the projected shortfall. The recommendations, which are expected by the end of the year, will initially focus on areas like joint initiatives with nonphysician oncology professionals and general practice physicians, modifications to oncology fellowship training programs, and guidance from ASCO on how oncology practices can improve efficiency.

By Carmen Phillips

The leadership of ASCO should be commended for sponsoring the AAMC report on the U.S. oncology work force. The conclusions they reach are clearly concerning: A potential shortage of 2,550 to 4,080 oncologists in the United States by 2020.

In many respects, the fact that a shortage is being projected is not surprising. We have known for some time that the population is aging and that, as a result, cancer incidence and prevalence are likely to increase. Using data from SEER and the SEER-Medicare Linked Database, NCI was able to generate specific projections of cancer prevalence and of the demand for oncology services through 2020. These data, combined with information on medical school graduation rates and reports from other specialty medicine groups about work force availability, raise concerns that there may be a shortage of oncologists over the next two decades.

With this new report, we now have a credible analysis from which the cancer and medical communities can begin to work together to address a serious situation, something ASCO is already doing with the assembly of an expert Workforce Implementation Group.

NCI’s contribution to this report was important, because it helped to quantify in the most accurate way possible the demand component of the analysis. We were able to do this because of NCI’s commitment to cancer surveillance research resources and personnel.

Dr. Angela Mariotto and colleagues from the Statistical Research Applications Branch in DCCPS used SEER data from 2000 to 2002 and applied it to the most recent U.S. Census Bureau population projections to develop a rigorous method for projecting incidence and prevalence for all cancers from 2000 through 2020. That work led to a forecast of a 48-percent increase in cancer incidence and an 81-percent increase in people living with or surviving cancer over this time period.

Dr. Joan Warren and colleagues from the Health Services and Economics Branch in DCCPS used data from the SEER-Medicare database to construct a model that separated out oncologist visit rates by patient sex, age, and time of diagnosis during patients’ first 12 months after diagnosis, last 12 months of life, and the period in between.

These analyses made it possible for the ASCO/AAMC study team to develop a clearer picture of important trends in cancer care, particularly the influence of increased cancer survivorship. These analyses revealed that two-thirds of the projected visits to oncologists in 2020 will be made by patients who are more than 1 year post-diagnosis.

That is likely due, in part, to the benefits being seen with adjuvant chemotherapy in breast and other cancers, and it means that, moving forward, oncologists will be involved in direct patient care with individual patients over longer periods of time. As a result, they may need to depend more on physician assistants and nurse practitioners and consult more closely with patients’ primary care physicians. Physician-patient communication and coordination of care, already topics of concern for U.S. health care delivery, will become even more important. Surveillance of such trends will be critical to a better understanding of the quality of cancer care and where, perhaps, efficiencies in care can be gained.

NCI staff are currently working on a paper for publication that will provide the technical details of how the demand projections that contributed to this important work force study were generated. In the interim, it’s gratifying to yet again witness the power of our surveillance program and contribute to an important new study that will help shape cancer care.

New Molecular Imaging Compound Pinpoints Metastases in Mice

Researchers have created a new imaging compound that fluoresces only when processed by cancer cells. Use of this compound allowed scientists to visualize 92 percent of the very small tumors in the peritoneum - the tissue that lines the wall of the abdomen - in mice with ovarian cancer. The results were published in the March 15 Cancer Research.

The team led by Dr. Hisataka Kobayashi from the Molecular Imaging Program in NCI’s Center for Cancer Research (CCR) created a compound consisting of the protein avidin, which binds to a protein commonly found on cancer cells that have spread to the peritoneum, joined to three molecules of the fluorescent compound rhodamine X. This complex, called Av-3ROX, is taken up by a cancer cell after binding to its surface and is subsequently broken down in the lysosome. When enzymes in the lysosome break the molecule into smaller pieces, the fluorescence from rhodamine X is released, enabling the cancer cell to be detected using imaging techniques.

To verify that Av-3ROX was specifically internalized into tumor cells, the investigators used cells that carried the gene for red fluorescent protein (RFP) to induce tumors and peritoneal metastases in mice. The investigators injected Av-3ROX into the peritoneum of the mice, captured fluorescent images of both Av-3ROX and RFP, and compared the number of metastases identified using both compounds. They found that Av3-ROX had 92 percent sensitivity and 98 percent specificity for the cancer cells.

Because Av-3ROX would cause an immune system reaction in humans, the researchers are now working on a second-generation compound that joins the binding site of avidin - the part that recognizes the cancer cells - to human serum albumin. The authors believe that this approach to molecular imaging “holds promise as a method of optically enhancing surgical or endoscopic procedures,” and may allow for more complete surgical removal of metastatic disease.

Many Protein Kinase Genes Linked to Cancer

Researchers have cataloged the mutations in genes that produce protein kinases, which are enzymes that regulate other proteins and play a role in some cancers. Using DNA from 210 diverse human cancers, the researchers sequenced 518 protein kinase genes. Approximately 120 of the genes carried a mutation related to cancer development and may function as cancer genes, the researchers reported in the March 8 Nature.

Drs. Andrew Futreal and Michael Stratton of the Wellcome Trust Sanger Institute in Cambridge, U.K., and their colleagues identified more than 1,000 mutations in the gene family, but only some of these are so-called “driver” mutations that drive the cancer. The others are “passenger” mutations, which are present in tumors but may not contribute to disease. Their results suggest that most mutations in cancer cells are likely to be passenger mutations.

Mutations were relatively common in cancers of the lung, stomach, ovary, colon, and kidney, and rare in cancers of the testis and breast. “Given that we have studied only 518 genes and limited numbers of each cancer type, it seems likely that the repertoire of mutated human cancer genes is larger than previously envisaged,” the researchers wrote.

Together with another large-scale sequencing study published in September 2006, this study presents a largely unbiased overview of the spectrum of mutations in human cancers, noted an editorial by Drs. Daniel Haber and Jeff Settleman of Massachusetts General Hospital. These studies suggest that “each cancer genome carries many unique abnormalities, and not all mutations identified contribute equally to the manifestation of the associated cancers,” they wrote.

Study Compares Two-Transplant Treatments

An Italian clinical trial has shown that patients with newly diagnosed multiple myeloma (MM) who received a transplant of their own stem cells (an autologous stem cell transplant) and a second stem cell transplant from an “HLA-matched” sibling (an allogeneic stem cell transplant) had superior survival outcomes compared to patients who received two autologous stem cell transplants.

Published in the March 15 New England Journal of Medicine, the trial involved 162 consecutive patients with newly diagnosed MM who were under age 65 and had at least 1 sibling. Patients with a sibling whose blood cells expressed genetically identical surface antigens, human-leukocyte antigens - known as an HLA match - were offered the option of the autologous-allogeneic treatment regimen. The chances of a sibling being an HLA match are one in four.

Both patient groups received the same initial chemotherapy regimen at conventional dosing followed by high-dose myeloablative chemotherapy and an autologous stem cell transplant. Those with an HLA-matched sibling received radiation and an allogeneic stem cell transplant using the siblings’ cells (60 patients); those without an HLA-identical sibling received another round of high-dose chemotherapy and a second autologous stem cell transplant (59 patients). Of these patients, 58 receiving allogeneic transplant and 46 receiving double autologous transplants completed treatment.

Allogeneic stem cell transplants, while they are considered to have greater curative potential because they have a stronger antitumor cell effect, have been associated with high treatment-related mortality rates. Combined regimens like the one used in the Italian trial that employ “reduced-intensity” chemotherapy or radiation before the allogeneic transplant “have lowered transplant-related mortality to approximately 15 percent,” lead author Dr. Benedetto Bruno of the University of Turin and colleagues explained. But it has been unclear whether they offer a survival advantage.

In the trial, there was little difference in treatment-related mortality between the two groups; however, survival outcomes clearly favored those in the autologous-allogeneic transplant group - a 67-percent improvement in overall survival and a 53-percent improvement in event-free survival.

African Americans' Prostate Mortality Rooted in Class

Prostate cancer mortality is twice as high in African American men compared with white men, a fact often attributed to poor education, lack of awareness of the threat, and undiscovered genetic factors.

In fact, according to a study published online March 12 in Cancer, screening, treatment choices, and health behavior are all affected by barriers that “arise directly from the racial disparity in socioeconomic position, not reduced information or culturally based misunderstandings sometimes presumed to arise in its wake.”

Dr. James A. Talcott of the Center for Outcomes Research at Harvard Medical School and colleagues surveyed 207 African American men and 348 white men from North Carolina who were recently diagnosed with prostate cancer. The disparities they found, generally attributed to lower social position, translate “into disadvantages in their medical care that may escape notice in studies that collect less detailed information than ours,” wrote the authors.

For example, the researchers found that African Americans were more aware than white men of their prostate cancer risk and the responsibility to get screened. Yet they were less able to access good medical care because of less convenient health care settings, less public and private insurance coverage, and less flexible work circumstances.

Distrust of their physicians was also rooted in African Americans’ health care experiences. Their lower income, educational level, and social status make them more likely to use public clinics and emergency rooms and less likely to receive continuity of care. They were also less likely to establish ongoing ties with a primary physician, had less frequent regular physical exams, and less follow-up on significant medical complaints. These findings led researchers to conclude that African Americans “are simply less likely to know their physicians and other providers well enough to develop trust.”

In passing the Mammography Quality Standards Act (MQSA) of 1992, Congress mandated efforts by the medical practice, research, and regulatory communities to improve the performance, quality assurance, and oversight of screening mammography in the United States. The Act authorized the Secretary of Health and Human Services to fund research establishing a breast cancer surveillance system that could assess more extensively mammography performance in clinical practice. Dr. Rachel Ballard-Barbash, associate director of DCCPS’ Applied Research Program, explains that “NCI was assigned the mandate for supporting this research and in response to the Act established the Breast Cancer Surveillance Consortium.”

Founded in 1994, BCSC originally consisted of independent centers studying the practice of breast cancer screening in their individual communities. However, it proved difficult to draw conclusive results from comparisons of similar but heterogenous data. NCI realized the potential of establishing an ongoing centralized database on women undergoing mammography, and increased the standardization of data collection and created a central pooled data resource from all of the centers. BCSC currently consists of five main research sites, two affiliated sites, and a statistical coordinating center located in Seattle, Washington.

“Because of the effort to create a pooled central research data resource, we now have data on over 5.5 million mammograms, representing over 2 million women. More than 52,000 cases of breast cancer have been diagnosed [at participating sites] over the 10 years that BCSC has been in operation,” says Dr. Ballard-Barbash.

This large, standardized dataset presents a unique opportunity for investigators throughout the country to study how mammography screening performance may be improved and how breast cancer screening relates to changes in disease stage at diagnosis, survival, and mortality. In addition, investigators have used BCSC to study disparities in screening and risk factors for breast cancer. It has also been used as a resource for new investigator-initiated studies. Researchers from any organization can apply to use BCSC data for their projects.

“This work produced to date includes more than 235 peer-reviewed publications on a variety of issues, including factors that affect the quality of mammography interpretation and breast characteristics, like density, that affect the likelihood of both cancer occurrence and detection,” says Dr. Stephen Taplin, project director of BCSC.

That breast density is a risk factor for breast cancer has become more widely known over the past several years, and this knowledge has been incorporated into several models for estimating an individual woman’s risk. A new study using BCSC data published in the March 7 Journal of the National Cancer Institute now adds an important piece of information on the use of breast density in calculating risk - that two or more measurements of density over time may be better at predicting risk than a single measurement.

The investigators, led by Dr. Karla Kerlikowske from the University of California, San Francisco, used prospectively collected data from 301,955 women aged 30 or older, who were not taking hormone-replacement therapy and had undergone at least two mammograms at a BCSC center. Breast density was scored on a scale of 1 to 4, in order of increasing density, by the American College of Radiology Breast Imaging Reporting and Data Systems (BI-RADS) criteria.

By linking BCSC records to cancer registry data, a capability built into BCSC data collection methods, the investigators identified 2,639 incidences of breast cancer in the group. Women diagnosed with breast cancer were more likely to have received a breast density score of 3 or 4 on their first and last mammogram than women without cancer. Overall, a high breast density score assigned on the first or last mammogram was associated with an increased likelihood of breast cancer.

Importantly, the rate of breast cancer diagnosis increased for women whose breast density score increased from first to last mammogram, and conversely decreased for most women whose breast density score decreased from first to last mammogram, with the exception that risk remained high for women with a breast density score of 4 on their first mammogram.

These results show “that breast density is a very important risk factor for breast cancer, and that because density can change over time, one measure at one point in time may not accurately reflect how breast density affects a woman’s risk of breast cancer,” explains Dr. Kerlikowske. “If you have two measurements over time, those two measurements together are more likely to give you a better idea of how density increases your risk.”

Dr. Kerlikowske and colleagues are now working on identifying the best time to measure a woman’s breast density for use in a risk model. This work and other BCSC collaborations, including projects in partnership with NCI’s Cancer Intervention and Surveillance Modeling Network and the American Cancer Society, will further leverage BCSC data to answer pressing questions about how best to use breast screening to help predict risk and reduce mortality, and how to improve mammography practices nationwide.

On March 9, the U.S. Food and Drug Administration (FDA) notified health care professionals of new safety information for drugs which stimulate red blood cell growth. The erythropoiesis-stimulating agents (ESAs) are Aranesp (darbepoetin alfa), Epogen (epoetin alfa), and Procrit (epoetin alfa). Four new studies in patients with cancer found a higher chance of serious and life-threatening side effects or death with the use of ESAs. These research studies were evaluating an unapproved dosing regimen, a patient population for which ESAs are not approved, or a new unapproved ESA. FDA believes these new concerns apply to all ESAs and is re-evaluating how to safely use this product class.

Complete information is available at http://www.fda.gov/medwatch/safety/2007/safety07.htm#ESA.

FDA Approves Lapatinib for Advanced Breast Cancer Patients

On March 13, FDA approved lapatinib (Tykerb), a new targeted anticancer treatment, to be used in combination with capecitabine (Xeloda) for patients with advanced or metastatic HER2-positive breast cancer. The combination treatment is indicated for women who have received prior therapy with other cancer drugs, including trastuzumab (Herceptin).

Additional information is available at http://www.fda.gov/bbs/topics/NEWS/2007/NEW01586.html.

Name of the Trial
Phase III Randomized Study of Palifermin for Reducing Oral Mucositis in Patients with Locally Advanced Squamous Cell Carcinoma of the Oral Cavity, Oropharynx, Hypopharynx, or Larynx Undergoing Concurrent Radiotherapy and Chemotherapy (RTOG-0435). See the protocol summary at http://cancer.gov/clinicaltrials/RTOG-0435.

Principal Investigator
Dr. David I. Rosenthal, Radiation Therapy Oncology Group 

Why This Trial Is Important
Nonsurgical treatment of locally advanced head and neck cancer usually involves a combination of radiotherapy and chemotherapy (chemoradiotherapy). Unfortunately, both the disease and its treatment are associated with serious oral complications. A common side effect of chemoradiotherapy is oral mucositis, inflammation of the mucous membranes in the mouth and throat that can cause painful sores. Severe oral mucositis can lead to delays in treatment, difficulty in eating and speaking, and life-threatening infections.

Palifermin has been approved by the FDA to prevent and treat mucositis in patients undergoing high-dose chemotherapy and radiotherapy for leukemia or lymphoma. It promotes the growth of mucosal cells lining the mouth and gastrointestinal tract and helps replace cells damaged by cancer treatment.

In this trial, patients undergoing chemoradiotherapy for advanced head and neck cancer will receive intravenous palifermin or placebo before and during cancer treatment.

Who Can Join This Trial
Researchers will enroll 298 patients with stage III or IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. See the list of eligibility criteria at http://cancer.gov/clinicaltrials/RTOG-0435.

Study Sites and Contact Information
Study sites in the United States are recruiting patients for this trial. See the list of study contacts at http://www.cancer.gov/clinicaltrials/RTOG-0435 or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237) for more information. The toll-free call is confidential.

If Memory Serves...

NCI’s first director was Dr. Carl Voegtlin, who served in this role from 1938 to 1943. He was born in Switzerland and received his Ph.D. from the University of Frieberg before coming to the United States in 1905. (Read more)

For more information about the birth of NCI, go to http://www. cancer.gov/aboutnci/ncia.

New Cancer Health Disparities Web Portal Launched NCI has just launched a Web portal on Cancer.gov to highlight the Institute’s efforts to reduce and ultimately eliminate cancer health disparities. The portal includes links to information about the NCI Center to Reduce Cancer Health Disparities, as well as information about training opportunities, statistics, and research resources and results. To view the portal, go to http://www.cancer.gov/health-disparities.

A Message to Our Readers Dear NCI Cancer Bulletin Subscribers: Beginning April 3, 2007, the NCI Cancer Bulletin will reduce its publication frequency to once every other week (or 24 issues per calendar year). This decision was reached following lengthy deliberations by the recently formed NCI Cancer Bulletin Executive Editorial Committee (EEC), which is composed of senior NCI scientists and leaders. The EEC is responsible for providing scientific advice and guidance on the newsletter’s content. This new schedule will give us the chance to create more in-depth articles and provide more perspective about the latest developments in cancer research. We on the NCI Cancer Bulletin staff are confident that readers will continue to find the same straightforward, high-quality science writing they have come to expect, as well as the latest cancer research news and information from NCI and other research organizations. In just 3 years, our circulation has increased to nearly 30,000 subscriptions - with more than 500 new readers signing up each month. We appreciate this growing interest in the NCI Cancer Bulletin and will continue to strive to meet the needs of old and new readers alike. - The Editors

Following are newly released NCI research funding opportunities:

Avon-NCI "Progress for Patients" Awards for Early Phase Clinical Interventions and Biomarkers in Breast Cancer (Limited Competitive Supplements [Revisions] for P30 Cancer Center Support Grants)
Announcement Number: PAR-07-244
Letter of Intent Receipt Dates: March 27 and Oct. 15, 2007
Application Receipt Dates: April 27 and Nov. 15, 2007

This funding opportunity will use the P30 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3690. Inquiries: Dr. Jaswant S. Bhorjee - bhorjeej@mail.nih.gov

CCR Grand Rounds March 27: Dr. William G. Nelson, Director, Molecular Pharmacology Laboratory; Professor of Oncology, Urology, Pharmacology, Medicine, Pathology & Radiation Oncology, The Johns Hopkins School of Medicine. “5-Me-CpG-Binding Domain Proteins and Prostate Cancer Detection, Diagnosis, Prevention, and Treatment.” April 3: Dr. Katherine A. Jones, Professor, The Salk Institute for Biological Studies. “Mechanistic Studies of RNAPII Transcription Elongation.” CCR Grand Rounds are held 8:30 to 9:30 a.m. at the NIH campus in Bethesda, MD, in the Clinical Center's Lipsett Amphitheater.

Avon-NCI "Progress for Patients" Awards for Early Phase Clinical Interventions and Biomarkers in Breast Cancer (Limited Competitive Supplements [Revisions] for P50 SPORE Grants)
Announcement Number: PAR-07-245
Letter of Intent Receipt Dates: March 27 and Oct. 15, 2007
Application Receipt Dates: April 27 and Nov. 15, 2007

This funding opportunity will use the P50 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3691. Inquiries: Dr. Igor Kuzmin - kuzmini@mail.nih.gov  

Technology Development for the Detection and Evaluation of Chemical and Biological Carcinogens (SBIR)
Announcement Number: PAS-07-240
Application Receipt Dates: April 5, Aug. 5, and Dec. 5, 2007

This funding opportunity will use the R43 and R44 award mechanisms. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3692. Inquiries: Phillip J. Daschner - pd93u@nih.gov

Technology for the Detection and Characterization of Low Abundance Proteins, Peptides, or Micro RNAs (SBIR)
Announcement Number: PAS-07-241
Application Receipt Dates: April 5, Aug. 5, and Dec. 5, 2007

This funding opportunity will use the R43 and R44 award mechanisms. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3693. Inquiries: Dr. J. Randy Knowlton - knowltoj@mail.nih.gov

Technologies and Software to Support Integrative Cancer Biology Research (SBIR)
Announcement Number: PAS-07-242
Application Receipt Dates: April 5, Aug. 5, and Dec. 5, 2007

This funding opportunity will use the R43 and R44 award mechanisms. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3694. Inquiries: Dr. Jennifer Couch - couchj@mail.nih.gov

2007 NIH Director’s New Innovator Award Program
Announcement Number: RFA-RM-07-009
Application Receipt Date: May 22, 2007

This funding opportunity will use the DP2 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3697. Inquiries: Dr. Judith H. Greenberg - newinnovator@nih.gov  

Occupational Safety and Health Research
Announcement Number: PA-07-318
New Application Receipt Dates: June 5 and Oct. 5, 2007; Feb. 5, June 5, and Oct. 5, 2008; Feb. 5, June 5, and Oct. 5, 2009; Feb. 5, 2010

This is a renewal of PA-04-038 and will use the R01 award mechanism. For more information, see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=3695. Inquiries: Dr. Mukesh Verma - vermam@mail.nih.gov