issue No. 26 / November 2012
cancer update Brenda Rabeno, MLS, MBA, prepares tissue samples for shipment.
in this issue Exploring Nanotechnology to Study Breast Cancer Putting Cancer Care Strategies Into Practice Patient Guides Offer Friendly Welcome Groundbreaking Salivary Gland Research Cancer Case Distribution Table
Helen F. Graham Cancer Center contributes to landmark breast cancer study with the Cancer Genome Atlas Project T HE H ELEN F. G RAHAM C ANCER is one of an elite group of institutions that provided tumor samples for groundbreaking research hailed as the largest, most comprehensive breast cancer genomic study ever. The results that are emerging from this landmark work are redefining our understanding of breast cancer, as well as other cancers, and signal a transformation in future treatments that will benefit a wide range of patients. Recent discoveries, published in the October issue of Nature, identify four genetically different subtypes of breast cancer, and within those, the genetic drivers of many different types of cancer. Researchers analyzed data from 825 breast tumor samples supplied by the Helen F. Graham Cancer Center and others as part of The Cancer Genome Atlas (TCGA) project. They identified at least 40 genetic alterations that could be targeted with anti-cancer drugs, many of which are being developed or used to treat other cancers with the same mutations. (continued on next page)
(continued from previous page)
l A N d m A r k b r e A s t CA N C e r s t u dy A surprising finding distinguishes a particularly poor prognosis for a breast cancer subtype found in the deep skin layer of basal cells linked to ovarian cancer. This opens up the possibility of routine treatment for ovarian cancer with some commonly available breast cancer drugs.
The Helen F. Graham Cancer Center is on a short list of TCGA tissue collection centers that includes major universities and leading hospitals such as MD Anderson Cancer Center, Memorial Sloan-Kettering Cancer Center and the Mayo Clinic. The Graham Center is one of only two National Cancer Institute (NCI) Community Cancer Centers chosen to participate. According to Dr. Petrelli, Christiana Care’s Tissue Procurement Center is the result of a highly coordinated effort. “We recognized almost a decade ago that our ability to collect, preserve and bank biospecimens would constitute an important research resource. Our success in building the Tissue Procurement Center was the result of teamwork and cooperation across disciplines that included our Cancer Program research staff, the departments of Pathology and Surgery, as well as operating room personnel.”
“We recognized almost a decade ago that our ability to collect, preserve and bank biospecimens would constitute an important research resource.” Nicholas J. Petrelli, M.D.
“The promise of TCGA is coming to fruition with unprecedented insights into the biology of cancer,” says Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center. “Our proven tissue procurement capability to match TCGA standards enables our contribution to this unprecedented effort to improve cancer therapies.” Reports from the TCGA project on similar studies of colon and lung cancer, in which the Graham Center also participated, were published in Nature in July and September. They pair colon and rectal tumors as a single type of cancer, not separate as previously thought, and identify potential new anti-cancer drug targets.
tissue collection supports research on cancer genetics The TCGA, funded by the National Institutes of Health, uses genomic technologies and large-scale gene sequencing to map out an atlas of genetic changes for specific types of cancers and shares that information publicly with scientists.
2 Christiana Care Health System
Today, the Tissue Procurement Center has banked about 3,000 human tissue specimens and, since 2009, has provided some 300 tissue samples to the TCGA for analysis. According to Tissue Procurement Manager Brenda Rabeno, MLS, MBA, these constitute most of the tumor types the TCGA accepts. “We have expanded our initial collection of brain, lung and ovarian tumors to include up to 20 additional tumor types,” she says. Cancer patients having surgery at Christiana Hospital who have not had prior chemotherapy or radiation can consent to donate a small sample of their tumor for TCGA research. Rabeno works hand in hand with the operating room teams and Pathology to identify tumors that meet TCGA requirements and collect small samples of the tumor not needed for diagnostic purposes. After a rigorous quality control process, the Tissue Procurement Center snap-freezes the tissue in 1-mL vials and ships it for analysis, along with the required documentation, a blood sample and sometimes normal tissue, to the TCGA Biospecimen Core Resource in Ohio. According to Rabeno, “The most exciting aspect of this project is that the genetic secrets unlocked in these small tissue samples are being pooled and shared with scientists whose work has already advanced the progress of cancer research.” References involving TCGA Team at the Helen F. Graham Cancer Center: 1. Molecular Characterization of Human Colon and Rectal Cancer. Nature. Vol. 487, p. 330, 2012. 2. Comprehensive Genomic Characterization of Squamous Cell Lung Cancer. Nature. Vol. 490, p. 519, 2012. 3. Comprehensive Molecular Portraits of Human Breast Cancers. Nature. Vol. 490, p. 61, 2012.
helen f. Graham Cancer Center scientist explores nanotechnology to study breast cancer STRANDS OF TINY, INTERWOVEN NANOFIBERS, BARELY VISIBLE TO THE NAKED EYE, COULD MAKE IT EASIER TO GROW BREAST CANCER STEM CELLS FOR STUDY IN THE LABORATORY.
Molecular biologist Jennifer Sims-Mourtada, Ph.D., Helen F. Graham Cancer Center senior clinical scientist for the Center for Translational Cancer Research (CTCR), is tracking the sonic hedgehog, a protein whose signature is linked to aggressive breast cancer. To succeed, she needs a continuous supply of robust cancer stem cells for study. “Breast cancer stem cells are difficult to reproduce in the Jennifer Sims-Mourtada, Ph.D. laboratory,” she explains. Recognized as the agents of tumor growth, cancer stem cells can divide and proliferate in unlimited numbers. However, growing them in a plastic Petri dish in the lab can cause them to behave and react differently than they normally would inside the human body. Seeking solutions, Dr. Sims-Mourtada is collaborating with Professor Eric Kmiec, Ph.D., chairman of the Department of Chemistry at Delaware State University. Dr. Kmiec’s lab has refined the art of spinning customized nanofiber webs, potentially the ideal environment to grow the stem cells Dr. Sims-Mourtada needs for her research.
3-d nanofiber scaffolds appealing Dr. Kmiec and his team have developed a way to create biodegradable nanofibers from scratch using a process called electrospinning. “The nanofibers offer a more natural, three-dimensional environment that seems to stimulate cell division and growth much closer to what actually happens in the human body,” he says. From their preliminary work, the team has determined that composition and dimension of the fibers appear to play a role in causing breast cancer stem cells to outgrow others in the mix of cells that populate a tumor. Encouraging the right kind of cells to repopulate is key for Dr. Sims-Mourtada’s research. Both she and Dr. Kmiec acknowledge that their work to achieve this has only just begun. However, in the future, she anticipates, “Nanowebs of viable stem cells could offer us a more reliable field for testing anti-cancer treatments. Potentially, we could use them to grow a patient’s own cancer cells to test and develop more individualized therapies.”
“We’ve learned that cancer stem cells like to grow when they are sitting on these fibers, like raindrops hanging from a spider web,” says Dr. Kmiec. No spider has ever spun a web this strong or this versatile. Breast cancer stem cells on nanofiber scaffolding.
“Nanowebs of viable stem cells could offer us a more reliable field for testing anti-cancer treatments.” Jennifer Sims-Mourtada, Ph.D.
Cancer Update 3
Putting commitment into practice:
two cancer care strategies that promote recovery and improve quality of life oNe:
knowing the risk for colon and other cancers can be a lifesaver
Personalized screening and management at the Helen F. Graham Cancer Center for patients with Lynch syndrome can potentially reduce the impact of associated cancers on health care dollars and, most importantly, improve longevity and quality of life. Genetic testing for Lynch syndrome in people with colorectal or endometrial cancer is a way to identify families with an increased risk of developing colon, rectal, endometrial and other cancers associated with Lynch syndrome. Knowing the risk is the first step toward prevention, early detection and prompt treatment.
what is lynch syndrome? Lynch syndrome runs in families. People who inherit one of the abnormal genes associated with Lynch syndrome lack the ability to repair minor mistakes in their genetic code or DNA. An accumulation of these mistakes can lead to cancer. There are two tests to identify Lynch syndrome: microsatellite instability (MSI) and immunohistochemistry (IHC). Because each study used alone has limitations, the Helen F. Graham Cancer Center’s Genetic Risk Assessment Program introduced a performance improvement strategy to use both tests to screen for Lynch syndrome in patients with colorectal or endometrial cancer. On the basis of the results, the team performed targeted DNA sequencing to identify high-risk families.
study findings As shown in Table 1 and Figure 1, of the 129 patients with colon cancer tested, 22 had abnormal results. Of these, one patient died and three declined services. Among the remaining 18, five had abnormal findings consistent with Lynch syndrome. The three who declined were suspected also to have Lynch syndrome. A genetic alteration in the BRAF gene associated with sporadic colon cancer was found in the other 13 patients. Of the 111 endometrial cancer patients tested, 24 had abnormal results. Additional studies are pending in nine patients. Of the remaining 15 patients, one (7%) had Lynch syndrome. The other 14 tested had hypermethylation of the MLH1 gene, thought to be associated with sporadic endometrial cancer. tAble 1: results for PAtieNts sCreeNed usiNG msi/ihC* testiNG CANCER TYPE
MSI/IHC ORDERED
ABNORMAL MSI/IHC
PERCENT ABNORMAL
ABNORMAL MSI/IHC EXCLUDING DECEASED AND PENDING FURTHER TESTING
LYNCH SYNDROME
PERCENT OF ABNORMAL THAT ARE LYNCH SYNDROME
COLON CANCER
129
22
17
21
8
36 (6.2% of total colon cancers tested)
ENDOMETRIAL CANCER
111
24
22
15
1
7 (0.9% of total endometrial)
4 Christiana Care Health System
*MSI – microsatellite instability / IHC – immunohistochemistry
fiGure 1. msi/ihC fiNdiNGs for PAtieNts sCreeNed by CANCer tyPe
two:
Giving cancer patients something to smile about
For patients with head and neck cancer, a pre-treatment dental exam can do more than protect a smile. A visit to the dentist can prevent complications, such as tooth decay or gum disease, that might jeopardize treatment or delay recovery.
129 111
22
24 8
1
moving forward The team will perform MSI/IHC testing on all colorectal and endometrial cancers that undergo surgical resection at Christiana Care. After one year, the team will re-evaluate the benefits and costeffectiveness of this strategy on the basis of the number of people determined to have Lynch syndrome and the number of additional family members who underwent genetic consultation or testing and were then stratified to high risk or low risk for cancers associated with Lynch syndrome.
A one-year study (Figure 2) of patients at the Helen F. Graham Cancer Center Multidisciplinary Head and Neck Oncology Clinic (MDC) confirmed that communication by the MDC nurse navigator and the introduction of standardized clearance forms shortened the time to initial dental visit and written dental clearance for treatment. fiGure 2. dAys to iNitiAl deNtAl visit ANd deNtAl CleArANCe Pre- (blue) ANd Post- (PurPle) iNterveNtioN
65.8%
10% DECREASE
DECREASE
f eAt ur e d e m P loy e e s
Patient Guides offer a friendly, helpful welcome The journey to a cure for cancer starts with first steps. For many, it is walking through the doors of the Helen F. Graham Cancer Center to a warm welcome from Patient Guides George Weaver and Richard Stout. “Interaction with patients and their families is the most important part of my job,” says Stout. “They inspire me to try to make their day a little bit better.” “Technically, our job is to make sure the patients get in and out of the Graham Center safely and that they know where they are going,” Weaver adds. “But it is really much more than that. Often we are the patient’s first contact. Seeing a smile and hearing a friendly voice helps put them at ease. Whatever we do to help is a good first step on their trip to getting well.” Richard Stout and George Weaver
Cancer Update 5
Spheroids of salivary gland cells releasing the enzyme alpha-amylase in a red stain to show their functionality.
Groundbreaking research moves forward to grow salivary glands RESEARCH TEAMS IN THE CENTER FOR TRANSLATIONAL CANCER RESEARCH (CTCR) at the Helen F. Graham Cancer Center are key players in a $2.5 million project, funded by the National Institutes of Health. The researchers are working on ways to grow human salivary glands in the lab. Ultimately, this could provide relief for thousands of patients who can no longer produce saliva as a result of radiation treatment for head and neck cancers. Principal investigator on the project is Robert Witt, M.D., chief of the Multidisciplinary Head and Neck Oncology Clinic at the Helen F. Graham Cancer Center. Nationally recognized for his work with salivary glands, Dr. Witt is the first Christiana Care physician to achieve the role of principal investigator for an NIH R01 grant through work done at Christiana Care. He is collaborating with Swati Pradhan Bhatt, Ph.D., a postdoctoral fellow at the University of Delaware, on ways to grow cells taken from patients before radiation on a threedimensional biomaterial-based scaffold that will mimic salivary gland functions. Although it could be 10 years or more away, ultimately doctors hope to be able to re-implant the patients’ own cells back into their damaged salivary glands when radiation is complete.
Magnified view of salivary spheroid growing hyaluronic-based hydrogel.
Robert Witt, M.D., and Swati Pradhan Bhatt, Ph.D. 6 Christiana Care Health System
ChristiANA CAre CANCer ProGrAm 2011 ANAlytiC* CAse distributioN YEAR SEEN BY CHRISTIANA CARE HEALTH SYSTEM PRIMARY SITE
2011 CASES BY AJCC STAGE GROUPS
2003
2004
2005
2006
2007
2008
2009
2010
2011
0
I
II
III
IV
Unk/NA
ORAL Lip Tongue Mouth Pharynx
52 0 19 27 6
60 3 10 34 13
67 1 21 35 10
51 2 18 23 8
68 3 26 26 13
73 1 25 40 7
78 4 26 41 7
87 3 29 44 11
74 0 25 34 15
3 0 2 0 1
16 0 7 6 3
5 0 1 2 2
9 0 1 5 3
36 0 12 19 5
5 0 2 2 1
DIGESTIVE Esophagus Stomach Small Intestine Colon Rectum/Rectosigmoid Liver Pancreas Other Digestive
425 34 29 9 191 69 29 47 17
418 32 31 14 157 72 22 63 27
401 15 32 7 171 67 21 63 25
444 18 35 8 178 81 29 67 28
460 29 35 8 168 76 35 69 40
498 36 34 16 179 80 30 83 40
442 29 25 15 158 68 32 77 38
433 20 32 13 155 72 36 69 36
473 39 30 18 138 74 36 85 53
6 0 0 0 6 0 0 0 0
93 7 7 1 32 21 9 8 8
110 8 8 2 37 27 2 17 9
106 10 6 1 39 17 6 13 14
116 10 8 8 22 8 9 39 12
42 4 1 6 2 1 10 8 10
RESPIRATORY Larynx Lung Other Respiratory Bone & Conn. Tissue Bone Connective Tissue Melanoma Other Skin Cancer
463 20 440 3 17 3 14 117 7
467 30 430 7 21 4 17 114 4
444 35 406 3 17 6 11 116 6
472 20 451 1 24 5 19 121 7
430 21 401 8 28 4 24 118 9
458 28 421 9 25 7 18 145 13
440 32 399 9 28 5 23 160 6
513 29 479 5 20 5 15 136 7
459 30 426 3 32 5 27 145 8
5 3 2 0 0 0 0 29 0
115 15 98 2 10 1 9 69 0
33 6 27 0 4 0 4 20 1
87 4 83 0 6 0 6 6 2
198 2 196 0 6 2 4 8 0
21 0 20 1 6 2 4 13 5
BREAST Female Organs Cervix Uterus Ovary Other Female Organs
556 184 27 90 49 18
488 196 31 97 53 15
557 182 37 98 41 6
534 194 27 103 47 17
597 229 48 113 54 14
639 198 33 101 37 27
703 228 41 110 52 25
652 202 41 110 39 12
698 257 33 154 53 17
181 3 0 2 0 1
261 140 15 106 10 9
156 18 5 6 7 0
58 37 6 12 16 3
21 46 7 17 19 3
21 13 0 11 1 1
MALE ORGANS Prostate Testis Other Male Organs
374 357 17 0
329 319 8 2
328 316 10 2
381 368 11 2
407 393 13 1
401 390 11 0
302 290 10 2
285 274 8 3
225 217 8 0
0 0 0 0
70 66 4 0
119 118 1 0
14 11 3 0
20 20 0 0
2 2 0 0
URINARY Bladder Kidney/Renal Pelvis Other Urinary
171 94 68 9
198 117 77 4
190 91 90 9
179 100 68 11
188 109 72 7
179 83 89 7
199 104 90 5
215 105 105 5
216 124 89 3
59 57 1 1
81 34 47 0
23 14 8 1
16 2 13 1
28 12 16 0
9 5 4 0
EYE
0
1
1
1
0
1
0
1
1
0
0
0
0
0
1
BRAIN/CNS
66
103
92
116
113
123
116
112
102
0
0
0
0
0
102
ENDOCRINE Thyroid Endocrine/Other
75 68 7
68 61 7
94 77 17
72 60 12
95 69 26
117 93 24
129 94 35
133 108 25
144 131 13
0 0 0
100 100 0
12 10 2
8 8 0
9 9 0
15 4 11
LEUKEMIA
28
43
58
60
68
79
37
53
57
0
0
0
0
0
57
OTHER HEMATOPOIETIC Hodgkin Non-Hodgkin Multiple Myeloma
147 23 102 22
130 6 103 21
137 23 96 18
145 18 102 25
138 10 102 26
189 20 130 39
174 20 126 28
147 25 97 25
151 15 108 28
0 0 0 0
41 5 36 0
23 7 16 0
28 1 27 0
27 2 25 0
32 0 4 28
ALL OTHER/UNDEFINED
90
69
55
62
67
80
70
86
72
0
0
1
3
3
65
2,772
2,709
2,745
2,863
3,015
3,218
3,112
3,082
3,114
286
996
525
380
518
409
TOTAL
*Analytic cases involve patients with new diagnoses or who were newly treated by Christiana Care Health System in 2011. Data source: Oncology Data Center. Prepared by R. McBride, CTR.
Cancer Update 7
Non-Profit Org. US Postage
PAID Wilmington, DE Permit No. 357
P.O. Box 1668 Wilmington, Delaware 19899 www.christianacare.org
One of the original 14 cancer centers in the nation selected for the National Cancer Institute Community Cancer Centers Program.
helen f. Graham Cancer Center research funding tops $5 million as a National Cancer institute Community Cancer Center THE HELEN F. GRAHAM CANCER CENTER IS AMONG 21 SELECTED NATIONALLY NATIONAL CANCER INSTITUTE (NCI) to continue as a member of the
BY THE
National Community Cancer Centers Program (NCCCP). This latest NCI grant raises total funding to just over $5.2 million, designated to create new research opportunities across the cancer care continuum. The NCCCP’s community-based platform supports basic, clinical and population-based research initiatives with emphasis on minorities and the underserved. NCCCP members collaborate to provide research-based cancer care from prevention and screening, through diagnosis, treatment, survivorship and end-of-life care. The Graham Center was among the very first selected in 2007 to participate as an NCI community cancer center. With funds from the American Recovery and Reinvestment Act, in 2010, NCI expanded from 16 community cancer Nicholas J. Petrelli, M.D. centers to 30 in 22 states. In July 2012, after a limited competition for additional funding, NCI selected the Graham Center among a streamlined number of participating hospitals to continue the program for an additional two years.
As A member of the NCCCP, the heleN f. GrAhAm CANCer CeNter is PArt of A NAtioNwide Network of hosPitAls studyiNG wAys to
Reduce cancer care disparities Increase clinical trial participation Improve cancer care quality Enhance cancer survivorship and palliative care services Broaden use of electronic health records and cancer research network connections Promote collection of high-quality biospecimens to support genomically informed research (also known as personalized medicine)
“Renewed funding means more patients will have access in their own community to the most advanced cancer treatments and early phase clinical trials,” says Nicholas J. Petrelli, M.D., Bank of America endowed medical director. “We are honored to be part of this elite national network as we continue to make progress in all aspects of cancer care.” Christiana Care is a private not-for-profit regional health care system and relies in part on the generosity of individuals, foundations and corporations to fulfill its mission. To learn more about how you can support our mission, please visit www.christianacare.org/donors. Cancer Update is produced by Christiana Care Health System. Entire publication © Christiana Care Health System, 2012. All rights reserved.
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