in this issue

issue No. 26 / November 2012

cancerupdate

(continued on next page)

Helen F. Graham Cancer Center contributes to landmark breast cancer studywith the Cancer Genome Atlas Project

THE HELEN F. GRAHAM CANCER is one of an elite group of institutions that providedtumor samples for groundbreaking research hailed as the largest, most comprehensivebreast cancer genomic study ever.

The results that are emerging from this landmark work are redefining our understandingof breast cancer, as well as other cancers, and signal a transformation in future treatmentsthat will benefit a wide range of patients.

Recent discoveries, published in the October issue of Nature, identify four geneticallydifferent subtypes of breast cancer, and within those, the genetic drivers of many differenttypes 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 samemutations.

Brenda Rabeno, MLS, MBA, prepares tissue samples

for shipment.

Exploring Nanotechnologyto Study Breast Cancer

Putting Cancer Care Strategies Into Practice

Patient Guides Offer Friendly Welcome

Groundbreaking Salivary Gland Research

Cancer Case Distribution Table

2 Christiana Care Health System

A surprising finding distinguishes a particularly poorprognosis for a breast cancer subtype found in the deepskin layer of basal cells linked to ovarian cancer. This opensup the possibility of routine treatment for ovarian cancerwith some commonly available breast cancer drugs.

“The promise of TCGA is coming to fruition withunprecedented insights into the biology of cancer,” saysNicholas J. Petrelli, M.D., Bank of America endowedmedical director of the Helen F. Graham Cancer Center.“Our proven tissue procurement capability to matchTCGA standards enables our contribution to thisunprecedented effort to improve cancer therapies.”

Reports from the TCGA project on similar studies of colon and lung cancer, in which the Graham Center alsoparticipated, were published in Nature in July andSeptember. They pair colon and rectal tumors as a singletype of cancer, not separate as previously thought, andidentify 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 genesequencing to map out an atlas of genetic changes forspecific types of cancers and shares that informationpublicly with scientists.

The Helen F. Graham Cancer Center is on a short list ofTCGA tissue collection centers that includes majoruniversities and leading hospitals such as MD AndersonCancer Center, Memorial Sloan-Kettering Cancer Centerand the Mayo Clinic. The Graham Center is one of only twoNational Cancer Institute (NCI) Community CancerCenters chosen to participate.

According to Dr. Petrelli, Christiana Care’s TissueProcurement Center is the result of a highly coordinatedeffort. “We recognized almost a decade ago that our abilityto collect, preserve and bank biospecimens wouldconstitute an important research resource. Our success inbuilding the Tissue Procurement Center was the result ofteamwork and cooperation across disciplines that includedour Cancer Program research staff, the departments ofPathology and Surgery, as well as operating roompersonnel.”

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 foranalysis. According to Tissue Procurement Manager Brenda Rabeno, MLS, MBA, these constitute most of thetumor types the TCGA accepts. “We have expanded ourinitial collection of brain, lung and ovarian tumors toinclude up to 20 additional tumor types,” she says.

Cancer patients having surgery at Christiana Hospitalwho have not had prior chemotherapy or radiation canconsent 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 tumorsthat meet TCGA requirements and collect small samplesof the tumor not needed for diagnostic purposes. After arigorous quality control process, the Tissue ProcurementCenter snap-freezes the tissue in 1-mL vials and ships itfor analysis, along with the required documentation, ablood sample and sometimes normal tissue, to the TCGABiospecimen Core Resource in Ohio. According toRabeno, “The most exciting aspect of this project is thatthe genetic secrets unlocked in these small tissue samplesare being pooled and shared with scientists whose workhas already advanced the progress of cancer research.”

(continued from previous page)

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.

“We recognized almost a decade agothat our ability to collect, preserve andbank biospecimens would constitute animportant research resource.”

Nicholas J. Petrelli, M.D.

l A N d m A r k b r e A s t C A N C e r s t u d y

Cancer Update 3

Molecular biologist JenniferSims-Mourtada, Ph.D., Helen F. Graham Cancer Centersenior clinical scientist for theCenter for Translational CancerResearch (CTCR), is tracking the sonic hedgehog, a proteinwhose signature is linked toaggressive breast cancer. Tosucceed, she needs a continuoussupply of robust cancer stemcells for study.

“Breast cancer stem cells aredifficult to reproduce in thelaboratory,” she explains.

Recognized as the agents of tumor growth, cancer stemcells can divide and proliferate in unlimited numbers.However, growing them in a plastic Petri dish in the labcan cause them to behave and react differently thanthey normally would inside the human body.

Seeking solutions, Dr. Sims-Mourtada is collaboratingwith Professor Eric Kmiec, Ph.D., chairman of theDepartment of Chemistry at Delaware State University.Dr. Kmiec’s lab has refined the art of spinningcustomized nanofiber webs, potentially the idealenvironment to grow the stem cells Dr. Sims-Mourtadaneeds for her research.

“We’ve learned that cancer stem cells like to grow whenthey are sitting on these fibers, like raindrops hangingfrom a spider web,” says Dr. Kmiec. No spider has everspun a web this strong or this versatile.

3-d nanofiber scaffolds appealing

Dr. Kmiec and his team have developed a way to createbiodegradable nanofibers from scratch using a processcalled electrospinning. “The nanofibers offer a morenatural, three-dimensional environment that seems tostimulate cell division and growth much closer to whatactually happens in the human body,” he says.

From their preliminary work, the team has determinedthat composition and dimension of the fibers appear to play a role in causing breast cancer stem cells tooutgrow others in the mix of cells that populate atumor.

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, sheanticipates, “Nanowebs of viable stem cells could offer us a more reliable field for testing anti-cancertreatments. Potentially, we could use them to grow apatient’s own cancer cells to test and develop moreindividualized therapies.”

helen f. Graham Cancer Center scientist explores nanotechnology to study breast cancer

STRANDS OF TINY, INTERWOVEN NANOFIBERS, BARELY VISIBLE TOTHE NAKED EYE, COULD MAKE IT EASIER TO GROW BREAST CANCERSTEM CELLS FOR STUDY IN THE LABORATORY.

“Nanowebs of viable stem cells could offer us a more reliablefield for testing anti-cancer treatments.”

Jennifer Sims-Mourtada, Ph.D.

Breast cancer stem cells onnanofiber scaffolding.

Jennifer Sims-Mourtada, Ph.D.

4 Christiana Care Health System

knowing the risk for colon andother cancers can be a lifesaver

Personalized screening and management at the Helen F. GrahamCancer Center for patients with Lynch syndrome can potentiallyreduce the impact of associated cancers on health care dollars and, mostimportantly, improve longevity and quality of life.

Genetic testing for Lynch syndrome in people with colorectal or endometrialcancer 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 Lynchsyndrome lack the ability to repair minor mistakes in their genetic code or DNA. An accumulation of thesemistakes 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 RiskAssessment Program introduced a performance improvement strategy to use both tests to screen for Lynchsyndrome in patients with colorectal or endometrial cancer. On the basis of the results, the team performedtargeted DNA sequencing to identify high-risk families.

Putting commitment into practice: two cancer care strategies that promoterecovery and improve quality of life

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 findingsconsistent with Lynch syndrome. The three who declined were suspected also to have Lynch syndrome. Agenetic 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 innine patients. Of the remaining 15 patients, one (7%) had Lynch syndrome. The other 14 tested hadhypermethylation of the MLH1 gene, thought to be associated with sporadic endometrial cancer.

tAble 1: results for PAtieNts sCreeNed usiNG msi/ihC* testiNG

oNe:

CANCER TYPE

MSI/IHC ORDERED

ABNORMALMSI/IHC

PERCENT ABNORMAL

ABNORMAL MSI/IHC EXCLUDINGDECEASED ANDPENDING FURTHERTESTING

LYNCH SYNDROME

PERCENT OF ABNORMAL THAT ARE LYNCH SYNDROME

COLON CANCER

129 22 17 21 8 36 (6.2% of total colon cancers tested)

ENDOMETRIALCANCER

111 24 22 15 1 7 (0.9% of total endometrial)

*MSI – microsatellite instability / IHC – immunohistochemistry

Cancer Update 5

fiGure 1. msi/ihC fiNdiNGs for PAtieNts sCreeNed by CANCer tyPe

moving forward

The team will perform MSI/IHC testing on all colorectal and endometrial cancers that undergosurgical resection at Christiana Care. After one year, the team will re-evaluate the benefits and cost-effectiveness of this strategy on the basis of the numberof people determined to have Lynch syndrome and thenumber of additional family members who underwentgenetic consultation or testing and were then stratifiedto high risk or low risk for cancers associated withLynch syndrome.

Giving cancer patientssomething 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 toothdecay or gum disease, that might jeopardize treatment or delay recovery.

A one-year study (Figure 2) of patients at the Helen F. Graham Cancer Center Multidisciplinary Head and Neck Oncology Clinic (MDC) confirmed thatcommunication by the MDC nurse navigator and the introduction of standardized clearance formsshortened 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% DECREASE

10% DECREASE

two:

Patient Guides offer a friendly, helpful welcome

The journey to a cure for cancer starts with first steps. For many, it iswalking through the doors of the Helen F. Graham Cancer Center to awarm welcome from Patient Guides George Weaver and Richard Stout.

“Interaction with patients and their families is the most important partof my job,” says Stout. “They inspire me to try to make their day a littlebit better.”

“Technically, our job is to make sure the patients get in and out of theGraham Center safely and that they know where they are going,”Weaver adds. “But it is really much more than that. Often we are thepatient’s first contact. Seeing a smile and hearing a friendly voice helpsput them at ease. Whatever we do to help is a good first step on theirtrip to getting well.”

feAtured emPloyees

Richard Stout and George Weaver

129

111

824

1

22

6 Christiana Care Health System

Principal investigator on the project is Robert Witt, M.D., chiefof the Multidisciplinary Head and Neck Oncology Clinic at theHelen F. Graham Cancer Center. Nationally recognized for hiswork with salivary glands, Dr. Witt is the first Christiana Carephysician to achieve the role of principal investigator for anNIH R01 grant through work done at Christiana Care.

He is collaborating with Swati Pradhan Bhatt, Ph.D., a post-doctoral fellow at the University of Delaware, on ways to grow cells taken from patients before radiation on a three-dimensional biomaterial-based scaffold that will mimic salivarygland 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 theirdamaged salivary glands when radiation is complete.

RESEARCH TEAMS IN THE CENTER FOR TRANSLATIONAL CANCER RESEARCH (CTCR) at theHelen F. Graham Cancer Center are key players in a $2.5 million project, funded by the NationalInstitutes of Health. The researchers are working on ways to grow human salivary glands in thelab. Ultimately, this could provide relief for thousands of patients who can no longer producesaliva as a result of radiation treatment for head and neck cancers.

Spheroids of salivary glandcells releasing the enzymealpha-amylase in a red stainto show their functionality.

Magnified view of salivary spheroidgrowing hyaluronic-based hydrogel.

Groundbreaking research moves forward to grow salivary glands

Robert Witt, M.D., and Swati Pradhan Bhatt, Ph.D.

Cancer Update 7

ChristiANA CAre CANCer ProGrAm 2011 ANAlytiC* CAse distributioN

YEAR SEEN BY CHRISTIANA CARE HEALTH SYSTEM 2011 CASES BY AJCC STAGE GROUPS

PRIMARY SITE 2003 2004 2005 2006 2007 2008 2009 2010 2011 0 I II III IV Unk/NA

ORAL 52 60 67 51 68 73 78 87 74 3 16 5 9 36 5Lip 0 3 1 2 3 1 4 3 0 0 0 0 0 0 0Tongue 19 10 21 18 26 25 26 29 25 2 7 1 1 12 2Mouth 27 34 35 23 26 40 41 44 34 0 6 2 5 19 2Pharynx 6 13 10 8 13 7 7 11 15 1 3 2 3 5 1

DIGESTIVE 425 418 401 444 460 498 442 433 473 6 93 110 106 116 42Esophagus 34 32 15 18 29 36 29 20 39 0 7 8 10 10 4Stomach 29 31 32 35 35 34 25 32 30 0 7 8 6 8 1Small Intestine 9 14 7 8 8 16 15 13 18 0 1 2 1 8 6Colon 191 157 171 178 168 179 158 155 138 6 32 37 39 22 2Rectum/Rectosigmoid 69 72 67 81 76 80 68 72 74 0 21 27 17 8 1Liver 29 22 21 29 35 30 32 36 36 0 9 2 6 9 10Pancreas 47 63 63 67 69 83 77 69 85 0 8 17 13 39 8Other Digestive 17 27 25 28 40 40 38 36 53 0 8 9 14 12 10

RESPIRATORY 463 467 444 472 430 458 440 513 459 5 115 33 87 198 21Larynx 20 30 35 20 21 28 32 29 30 3 15 6 4 2 0Lung 440 430 406 451 401 421 399 479 426 2 98 27 83 196 20Other Respiratory 3 7 3 1 8 9 9 5 3 0 2 0 0 0 1Bone & Conn. Tissue 17 21 17 24 28 25 28 20 32 0 10 4 6 6 6Bone 3 4 6 5 4 7 5 5 5 0 1 0 0 2 2Connective Tissue 14 17 11 19 24 18 23 15 27 0 9 4 6 4 4Melanoma 117 114 116 121 118 145 160 136 145 29 69 20 6 8 13Other Skin Cancer 7 4 6 7 9 13 6 7 8 0 0 1 2 0 5

BREAST 556 488 557 534 597 639 703 652 698 181 261 156 58 21 21Female Organs 184 196 182 194 229 198 228 202 257 3 140 18 37 46 13Cervix 27 31 37 27 48 33 41 41 33 0 15 5 6 7 0Uterus 90 97 98 103 113 101 110 110 154 2 106 6 12 17 11Ovary 49 53 41 47 54 37 52 39 53 0 10 7 16 19 1Other Female Organs 18 15 6 17 14 27 25 12 17 1 9 0 3 3 1

MALE ORGANS 374 329 328 381 407 401 302 285 225 0 70 119 14 20 2Prostate 357 319 316 368 393 390 290 274 217 0 66 118 11 20 2Testis 17 8 10 11 13 11 10 8 8 0 4 1 3 0 0Other Male Organs 0 2 2 2 1 0 2 3 0 0 0 0 0 0 0

URINARY 171 198 190 179 188 179 199 215 216 59 81 23 16 28 9Bladder 94 117 91 100 109 83 104 105 124 57 34 14 2 12 5Kidney/Renal Pelvis 68 77 90 68 72 89 90 105 89 1 47 8 13 16 4Other Urinary 9 4 9 11 7 7 5 5 3 1 0 1 1 0 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 75 68 94 72 95 117 129 133 144 0 100 12 8 9 15Thyroid 68 61 77 60 69 93 94 108 131 0 100 10 8 9 4Endocrine/Other 7 7 17 12 26 24 35 25 13 0 0 2 0 0 11

LEUKEMIA 28 43 58 60 68 79 37 53 57 0 0 0 0 0 57

OTHER HEMATOPOIETIC 147 130 137 145 138 189 174 147 151 0 41 23 28 27 32Hodgkin 23 6 23 18 10 20 20 25 15 0 5 7 1 2 0Non-Hodgkin 102 103 96 102 102 130 126 97 108 0 36 16 27 25 4Multiple Myeloma 22 21 18 25 26 39 28 25 28 0 0 0 0 0 28

ALL OTHER/UNDEFINED 90 69 55 62 67 80 70 86 72 0 0 1 3 3 65

TOTAL 2,772 2,709 2,745 2,863 3,015 3,218 3,112 3,082 3,114 286 996 525 380 518 409

*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 is produced by Christiana Care Health System. Entire publication © Christiana Care Health System, 2012. All rights reserved. 13CANC12

Christiana Care is a private not-for-profit regional health care system and relies in part on the generosity of individuals, foundations andcorporations to fulfill its mission. To learn more about how you can support our mission, please visit www.christianacare.org/donors.

P.O. Box 1668Wilmington, Delaware 19899www.christianacare.org

One of the original 14 cancer centersin the nation selected for the

National Cancer Institute CommunityCancer Centers Program.

Non-Profit Org.US Postage

PAIDWilmington, DEPermit No. 357

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

BY THE NATIONAL CANCER INSTITUTE (NCI) to continue as a member of theNational Community Cancer Centers Program (NCCCP). This latest NCI grantraises total funding to just over $5.2 million, designated to create new researchopportunities across the cancer care continuum.

The NCCCP’s community-based platformsupports basic, clinical and population-basedresearch initiatives with emphasis on minoritiesand the underserved. NCCCP memberscollaborate to provide research-based cancer carefrom prevention and screening, throughdiagnosis, treatment, survivorship and end-of-lifecare.

The Graham Center was among the very firstselected in 2007 to participate as an NCIcommunity cancer center. With funds from theAmerican Recovery and Reinvestment Act, in2010, NCI expanded from 16 community cancercenters to 30 in 22 states. In July 2012, after a

limited competition for additional funding, NCI selected the Graham Centeramong a streamlined number of participating hospitals to continuethe program for an additional two years.

“Renewed funding means more patients will have access in theirown community to the most advanced cancer treatments and earlyphase clinical trials,” says Nicholas J. Petrelli, M.D., Bank ofAmerica endowed medical director. “We are honored to be part ofthis elite national network as we continue to make progress in allaspects of cancer care.”

Nicholas J. Petrelli, M.D.

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 andpalliative care services

Broaden use of electronic healthrecords and cancer research networkconnections

Promote collection of high-qualitybiospecimens to support genomicallyinformed research (also known aspersonalized medicine)