OP Winter-Spring AR 2005 · Title: OP Winter-Spring AR 2005 Created Date: 10/8/2008 5:28:52 PM

F a l l / W i n t e r 2 0 0 8

Research and Care at Dana-Farber Cancer Institute

A LEADINGEXAMPLE

HOW PATIENTS TAKECENTER STAGE WITH THEIR

POWERFUL MESSAGE

DEFINING “CURE” • BATTLING LUNG CANCER • PATHOLOGY’S CRITICAL ROLE

More than half a century of scientific and clini-cal advances have changed the way canceris perceived by the general public and the

medical community. Prior to World War II, physicianswidely believed that cancers could not be thwarted bychemical-based medicines, a bias shattered in the late1940s when Dana-Farber founder Dr. Sidney Farberdemonstrated that drugs could produce remissions inchildhood leukemia. In the intervening years, treat-ments and survival rates have improved to the pointwhere a number of cancers are viewed as conditionsthat can be controlled, contained, and treated as chronicillnesses – often for many years, with a high quality oflife. Too many others, unfortunately, still defy our bestefforts to improve survival. However, the overall out-look is brightening every day.As an article in this issue of Paths of Progress asks,

what will a cure for cancer look like? Based on all thetrends we can discern in the laboratory and the clinic,it’s clear that a cure won’t take the form of a singleagent that can quell all of the roughly 400 related con-ditions that go by the name ‘cancer.’ Cancer is toocomplicated a disorder at both the molecular and largerbiological level for any “magic bullet” approach. Morelikely, as our understanding of the genetic directivesunderlying cancer grows, a variety of individualizedtreatments will be needed to strike the multiple weak

From the President

Copyright © 2008 Dana-Farber Cancer Institute. All rights reserved.

points in tumors’ molecular makeup. Still, it is a sign ofhow far we have come, and how confident we have rea-son to be, that we can speak of conquering a conditionthat once instilled such universal fear that its name wasrarely spoken.As a group, the stories in this issue can be thought of

as offering a mid-course look at how the journey towardcures is faring. The pieces on lung cancer research andcancer pathology illustrate the state of the art in thesetwo areas. The articles on the Patient and FamilyAdvisory Councils and the physical and emotional upsand downs of living with cancer focus on the personalside of disease, exploring how patients call on their cop-ing skills and sometimes direct their energy towardimproving the care they and others receive.Although it is impossible to know how cancer treat-

ment will evolve and be refined in the years ahead, wedo know that patients – as advocates, participants inclinical trials, and teachers about the human spirit – willbe the true heroes in the process. I hope you enjoy read-ing about our progress.

PATHS OF PROGRESS Fall/Winter 2008

Volume 17, Number 2

President, Dana-Farber Cancer Institute Edward J. Benz Jr., MD

Chief Medical Officer Lawrence N. Shulman, MD

Chief Scientific Officer Barrett J. Rollins, MD, PhD

Chief Clinical Research Officer Philip W. Kantoff, MD

Chief of Staff Stephen E. Sallan, MD

Chair, Medical Oncology James D. Griffin, MD

Chair, Pediatric Oncology Stuart H. Orkin, MD

Chair, Radiation Oncology Jay R. Harris, MD

Chair, Executive Committee for Research David M. Livingston, MD

Senior VP for Experimental Medicine Lee M. Nadler, MD

Senior VP for Patient Care Services, Chief Nurse Patricia Reid Ponte, RN, DNSc, FAAN

Senior VP for Research Beverly R. Ginsburg-Cooper, MBA

Edward J. Benz Jr., MDPresident, Dana-Farber Cancer Institute

Senior VP for Communications Steven R. Singer

Editor Michael Buller

Design John DiGianni

Associate Editor Robert Levy

Articles Editor Saul Wisnia

Contributors Christine Cleary, Cindy Hutter, Prashant Nair, Debra Ruder,Richard Saltus, Dawn Stapleton

Production Assistance Patricia Cleary, Jacqueline Czel, Molly Gillette,Kimberly Regensburg, Lee Whale

Photography Sam Ogden, Joshi Radin, Getty Images

Paths of Progress is published twice a year by Dana-Farber Cancer Institute’sDepartment of Communications. If you have any comments or would like to beremoved from the mailing list, please contact:

Michael Buller, Editor, Paths of ProgressDana-Farber Cancer Institute, Department of Communications44 Binney Street, Boston, MA 02115-6084(617) [email protected]

www.dana-farber.org

8 What Is a Cure?By Richard SaltusAdvances in research and in our understanding of its underpinningsare changing how we talk about treating and curing cancer.

13 Ups and DownsBy Saul WisniaWith support and understanding from friends, family, and caregivers,patients navigate the many obstacles on the road to recovery.

16 Lung DistanceBy Rob LevyAs researchers unravel the genetic mysteries of lung cancer, they’reextending the reach of treatment for the disease.

22 Leading theWayBy Christine ClearyFor 10 years, members of the Patient and Family Advisory Councilshave been tireless advocates for the power of patient-familycentered care.

26 Journey to the Center of DiagnosisBy Prashant NairOn its travels from laboratory to laboratory, a tumor leaves behinda critical trail of knowledge, discovery, and diagnosis.

30 First Person: Cori Liptak, PhDEdited by Dawn StapletonSenior psychologist Cori Liptak, PhD, talks about the vital role thepsychosocial clinician plays in treating both pediatric patients andtheir families.

Departments:

Dateline, page 2Including: Crafting cancer legislation, an award for Dana-Farber’spatient-centered care, and the growing field of pyschosocialoncology and palliative care.

Discoveries, page 6Including: The promise of targeted therapies, two studies on coloncancer risk, and a new mathematical tool for cancer genes.

ContentsFall/Winter 2008

2 PAT H S O F P R O G R E S S Fall/Winter 2008

news around the Institute

Dana-Farber President Edward J. Benz Jr., MD, ishelping shape legislation that aims to reenergize andreengineer the nation’s war on cancer.A developing bill, co-sponsored by Sens. Edward

Kennedy (D-Mass.) and Kay Bailey Hutchison(R-Texas), seeks to overhaul the 1971 National CancerAct by improving the coordination of cancer research,prevention, and treatment, and by expanding fundingto the National Cancer Institute. The senators solicitedthe advice of Benz, who calls for a more holisticapproach to the fight against cancer, one that promotescollaboration among research centers and hospitals,insurers, foundations and advocacy groups, privateindustry, and government.“We need to make research part of each and every

initiative and intervention associated with cancer,whether it’s basic biological research, public health,nursing, or clinical research,” says Benz, who wasinvited by Kennedy to speak at a U.S. SenateCommittee hearing in May titled “Cancer: Challenges

and Opportunities in the 21st Century.”Benz also notes the importance of increasing access to

cancer care, especially among traditionally underservedgroups, and raising participation in clinical trials byencouraging private and government insurers to pay thebasic medical costs of trial participants.Dana-Farber’s involvement with a national bill speaks

to Benz’s position as a leader in the oncology field; heserves as president of the Dana-Farber/Harvard CancerCenter and the Association of American CancerInstitutes, which represents 92 comprehensive cancercenters. Benz also co-chairs the Research WorkingGroup, a panel of scientists, physicians, and policy advo-cates that recently surveyed the body of cancer researchcurrently being conducted in the U.S.The Senate committee is considering new cancer legis-

lation at a time when federal funding for independentinvestigators is leveling off, potentially hampering thepace of cancer research. Legislators plan to send the billto the full Senate and House of Representatives in 2009.

Crafting cancer legislation

New academic department supports growing fieldsThe growing depth and breadth of services in psy-

chosocial oncology and palliative care at Dana-Farberhas led to the creation of a joint academic departmentfor these areas.The new Psychosocial Oncology and Palliative

Care department, which is chaired by Susan Block,MD, a recognized leader in these fields, brings to-gether several separate adult and pediatric programs,many of which share common clinical, practice, andresearch concerns.Psychosocial oncology caregivers provide support for

handling anxiety and sadness, depression, changes inthinking and behavior, and personal and spiritual issuesthrough all phases of the cancer experience. Palliative

care specialists focus on managing pain and other phys-ical symptoms, along with emotional concerns anddecision-making challenges that patients and their fami-lies face as they cope with a life-threatening illness.Though the two areas’ services are unique, they havethe same objective: helping patients and families main-tain the best quality of life.“Our goal, through collaboration among our services,

is to support our clinicians, amplify our impacton patients, and create a national model for care,”says Block.A compelling reason to form the new department,

according to Dana-Farber President Edward J. BenzJr., MD, was that the size and scope of activities and

Dana-Farber President Edward J. Benz Jr., MD, testifiesat a U.S. Senate Committee hearing this spring.

Dateline

Dana-Farber cited as role model in partnering with patients

Fall/Winter 2008 PAT H S O F P R O G R E S S 3

Dana-Farber’s efforts to involve patients and theirfamilies in clinical caregiving were recognized in Aprilwith the Blue Cross Blue Shield of Massachusetts(BCBSMA) Health Care Excellence Award.In bestowing the honor, which carries a $100,000

award, a panel of national and local leaders in healthcare delivery cited Dana-Farber as a pioneer in engagingand empowering patients in every aspect of care, fromthe bedside to the boardroom.“One of the ways to improve our health care system

is to recognize and support organizations that canguide us to exceptional achievement in creating andimplementing innovative programs and partnerships,”says Cleve Killingsworth, BCBSMA’s chairman andCEO. “Dana-Farber has transformed the delivery ofcare through its entire organization by encouragingcollaboration, communication, and engagement withpatients – activities that are critical to ensuring that thequality of health care in Massachusetts remains of thehighest standard.”More than 30 organizations submitted nominations for

the award, which was established in 2007 to recognizeorganizations that excel in improving the safety andeffectiveness of health care in the Commonwealth.Using the occasion of this recognition to recommit

the Institute to safe, patient- and family-centered care,DFCI President Edward J. Benz Jr., MD, launcheda set of initiatives “to ensure that both our culture of

safety and our safety practices will remain the best thatcan possibly be achieved.” Highlights include:

• Opening adult clinics earlier, so patient check-instarts at 7 a.m. to accommodate more people.

Clinical staff like Latoya Toney-Morris are spreadingpatient appointments more evenly throughout the day.

personnel have grown rapidly in these patient-careareas. The Institute also conducts a wide array of edu-cation programs and research on cancer-related mentalhealth issues.“What were small programs only a few years ago

have become internationally respected and leaders inthe field,” says Benz.Dana-Farber faculty who work in psychosocical

oncology and palliative care will be part of an inter-

disciplinary group with a common mission. The depart-ment will also provide a single point of connectionbetween the mental health and palliative care facultiesand their academic homes in Adult or Child Psychiatry,Medicine, and Pediatrics, create opportunities forcollaborations, and assure that the perspectives andinterests of psychosocial oncology and palliative carefaculty members are appropriately represented in theInstitute’s academic councils.

Continued on next page

news around the Institute


Dana-Farber pediatric oncologist David Pellman, MD,was named one of 56 new Investigators by the HowardHughes Medical Institute (HHMI), one of thenation’s largest philanthropies and supporters of bio-medical research, in May. HHMI holds nationwidecompetitions to select scientists who are at a relatively

Pediatric researchers top list of recent faculty honors

• Creating new scheduling guidelines and systems tohelp spread out the peak of patient volume.

• Adding more infusion chairs, exam rooms, and staff.

• Increasing the number of DFCI patients seen at theFaulkner Hospital satellite clinic and the cancercenter at Milford Regional Medical Center.Preparations are also under way for new sites inWeymouth, Mass., and Londonderry, N.H.

• Appointing Sharon Lane, RN, MSN, as the newassociate director of the Center for Patient Safety

and creating a new medication safety officerposition in the Pharmacy.

• Establishing a new training program to build moreeffective and collaborative clinical teams.

• Surveying front-line staff about their perceptions andrecommendations about patient safety, and developinga new online education program.

• Deploying two Information Services initiatives toreduce the risk of human error in computerizedclinical systems.

Pediatric oncologist David Pellman received national recog-nition for his groundbreaking research on aneuploidy.

early stage in their careers, highly productive, and pursu-ing groundbreaking research.Pellman studies aneuploidy, the abnormal chromo-

some numbers often observed in cancer cells. Workingwith yeast and mouse models, Pellman and colleaguesdiscovered an important route to aneuploidy andcancer: doubling the entire set of chromosomes (alsoknown as polyploidy).“The idea that the doubling of the genome would

contribute to tumor development is one of those ideasthat’s been out there, would get revisited every 10 yearsor so, but would then be forgotten,” says Pellman,who hopes to develop new treatment approaches thatexploit the biological differences between normal andaneuploid cells.In another honor, the Society for Pediatric Research

recently awarded an E. Mead Johnson Award to ToddGolub, MD, for his pioneering work in cancergenomics. Golub, a Dana-Farber and Children’s HospitalBoston pediatric oncologist, also directs the cancer pro-gram at the Broad Institute of Harvard and MIT. He isbest known for developing new technology for usingmRNA and microRNA expression profiles, which indi-cate activity levels of different genes, to classify cancersand predict their behavior.Most recently, Golub established an entirely new way

to use gene expression data to identify drugs that mimic

Dateline


Several Dana-Farber faculty mem-bers were honored at the AmericanSociety of Clinical Oncology’s(ASCO) annual meeting in thespring. Bruce Johnson, MD, directorof the Lowe Center for ThoracicOncology, took home a new ASCOhonor, the Translational ResearchProfessorship. It is designed to sup-port oncologists dedicated to bringingadvances in basic sciences into clini-cal practice and to mentoring othertranslational researchers. He wasalso named to the ASCO Board ofDirectors. Jay Harris, MD, chair of

Multiple societies honored cancer genomic pioneerTodd Golub.

or oppose genetic changes induced by disease. Thetechnique analyzes changes in gene expression ofdiseased versus normal cells, and compares themwith similar changes induced by a battery of FDA-approved drugs.Golub’s translational research accomplishments were

further recognized with his recent election to theAmerican Society for Clinical Investigation. Thesociety acknowledges the achievement of scientistswho have leveraged laboratory findings into advancesin medical care.

the Radiation Oncology Department,was named winner of the annualGianni Bonadonna Breast CancerAward for his outstanding achieve-ments in breast cancer researchand treatment.Elizabeth Cooley, RN, BSN; Lisa

Doherty, RN, NP; Bette JeanneKelly, RN, MS; Jeannine Sudol,RN, BSN; and AnnetteWerger, NP,MS, were selected from a field ofhundreds across the state to be rec-ognized for their special work in TheBoston Globe’s sixth annual Saluteto Nurses. The DFCI caregivers

Green efforts earn statewide recognitionDana-Farber was named the 2008 Green Binny

Institutional/Non-Profit of the Year in October. Thestatewide honor, by the Massachusetts RecyclingCoalition, is given annually to an organization thatshows leadership in recycling and waste reduction.“The Institute is committed to protecting natural

resources, reducing waste, and promoting a healthyenvironment for patients, employees, and visitors. Thisaward is evidence that our efforts are working,” saysDFCI’s Director of Environmental Health and Safety

Melissa McCullough, MS, CHMM, CIH.The Green Binny is one of several environmental

awards that Dana-Farber has earned in recent years. TheInstitute has won two merit awards and a WasteWisePartners of the Year award from the U.S. EnvironmentalProtection Agency. It’s also been recognized byHospitals for a Healthy Environment (H2E) for its suc-cess in reducing the use of products with mercury andthe release of mercury waste, and by the City of Bostonfor being a bike-friendly business.

were nominated by patients or fami-lies for the honor.Marsha Fonteyn, RN, PhD, is this

year’s recipient of Nursing Spectrummagazine’s Excellence Award formentoring in New England. SusanDeCristofaro, RN, MS, director ofPatient and Family Education, andLinda Pellerin, RN, MSN, clinicalnurse specialist, were finalists in thecommunity service and teaching cate-gories, respectively. The awards sup-port and celebrate nurses who shinein clinical care, community service,management, mentoring, and teaching.

Additional awards and honors


Discoveries at the Institute

Two recent studies by Dana-Farber scientists provide additionaldetails about who is at increasedrisk for colorectal cancer andwho may have the best chanceof surviving it.One study found that having a

family history of colon or rectalcancer doubles one’s risk of devel-oping the disease but also improvesthe odds of survival if the cancerdoes occur. Researchers, led byJennifer Chan, MD, MPH,Charles Fuchs, MD, MPH, andJeffrey Meyerhardt, MD, MPH,found that patients treated foradvanced, stage 3 colorectal cancerfared significantly better if they had

Research sharpens picture of colon cancer riska first-degree relative (parent,sibling, or child) with the diseasethan if they had no such familyhistory. The investigators don’t fullyunderstand why this is the case buthope further research will revealthe answer.The second study reported that

people diagnosed with colon cancerwho had abundant vitamin D in theirblood were less likely to die during afollow-up period than those whowere deficient in the vitamin. Thefindings are intriguing, but studyleaders Kimmie Ng, MD, MPH, andFuchs say further studies are neededto examine whether supplements canbenefit colorectal cancer patients. Colon cancer cells

The future of personalized cancertherapy came into sharper focusthis spring when Dana-Farberresearchers achieved a medical

Success of drug in melanoma patient burnishespromise of targeted therapies

first – using a “targeted” drugto drive a patient’s metastaticmelanoma into remission.The case involved a 79-year-old

woman who had several melanomatumors in her abdomen. When labtests showed the tumor cells carriedan abnormality in a gene calledKIT, the patient enrolled in a clini-cal trial involving Gleevec®, a drugknown to target that gene. Fourweeks after she began therapy,imaging exams showed a dramaticreduction in tumor size and activity.Four months later, the tumors werestill in check.“This is the first proof of princi-

ple that we can find an Achilles’ heel”– a gene critical to tumor cell growthand proliferation – “in melanoma and,by targeting that gene with a drug,cause the cells to die,” says Dana-Farber’s Stephen Hodi, MD, wholed the study. “It is especiallysignificant because there haven’t beenany effective treatments for melanomapatients with metastatic disease.”Because KIT mutations are found in

only a small percent of melanomas,Gleevec does not represent a universaltreatment for the disease. But the casesuggests that drugs that target othergene abnormalities in melanoma cellsmay be equally successful.Stephen Hodi


New research is shedding lighton patients’ concerns and prefer-ences when diagnosed with cancerand when completing trials ofnew treatments.In one study, Dana-Farber investi-

gators found that elevated levels ofanxiety may cause women withductal carcinoma in situ (DCIS),the most common form of non-invasive breast cancer, to overesti-mate their risk of recurrence or ofdying from breast cancer.“Although DCIS typically is

a very treatable disease, manywomen diagnosed with it developinaccurate risk perceptions,” saysAnn Partridge, MD, MPH, wholed the study with Dana-Farber col-league EricWiner, MD. “Thisexaggerated sense of risk needs to

Patients’ worries and wishes gain attentionbe addressed, as it may causewomen to make poor treatmentchoices and adversely affect theiremotional well-being and subse-quent health behaviors.”In a second study headed up by

Partridge and Winer, an over-whelming majority of patients par-ticipating in clinical trials to testnew therapies said they’d like toreceive reports of the trial out-comes. These results countered theconventional view that such infor-mation would cause patients anxi-ety and confusion.“We can share results safely,”

says Partridge. “Patients appreciatelearning them, and it doesn’t inter-fere with the clinical trial processin any negative way, as far as wecould detect.”

The advent of technology forscanning thousands of genes ata time to see which are mutatedin cancer cells has presentedresearchers with a downpour ofdata – and a quandary. How tosort through the dozens or evenhundreds of genes that oftenturn up abnormal on such scansto determine which are trulyinvolved in cancer, and whichare merely decoys?Investigators at Dana-Farber

and Memorial Sloan-KetteringCancer Center have developed aset of mathematical formulas, or

Mathematical tool searches for cancer genesan algorithm, to do just that. Thealgorithm, now freely available toscientists online, ranks genes bytheir likelihood of being involvedin cancer. In a study published thisspring, the researchers showedthat a gene identified by the algo-rithm as a likely tumor restrainerindeed plays that role in a com-mon type of brain cancer, and isnot a mere “bystander” to anotherrestrainer gene.The algorithm promises to

be especially valuable to TheCancer Genome Atlas (TCGA)pilot project, a federally led effort

to explore genomic changes linkedto human cancer, according toDana-Farber’s Lynda Chin, MD,senior author of the study and aleading participant in TCGA.

“As the project begins to mapthe genetic alterations in differentkinds of cancer, we need to be ableto discriminate between alterationsthat truly are relevant to the dis-ease and those that are not,” shesays. “The new algorithm, whichwas developed in collaborationwith Dr. Cameron Brennan ofMemorial Sloan-Kettering, willhelp us do that.”

Eric Winer and Ann Partridge


What isaCure?

By Richard Saltus

Not so long ago, cancer wasso feared that many darednot say its name: “The

Big C,” they called it. These days,people speak much more openlyand the disease has lost some of itsstigma and death-sentence aura.Treatments are better, mortalityrates are falling, and incidencerates for some forms of cancerare declining.Now another “C” word bubbles

up often in the cancer community –“the cure.” It’s hardly a new word,of course: A “cure for cancer” haslong been near the top of human-kind’s wish list. The earliest docu-

mented case of cancer, recorded onpapyrus in about 1,500 BC inEgypt, was treated by burning witha hot iron. The ancient physiciansopined that the disease was not cur-able. But with the explosion ofknowledge about cancer beginningin the mid-20th century, optimismsurged. In the 1970s, for example,the American Cancer Society (ACS)used a slogan, “We want to wipeout cancer in your lifetime.”Today, “For the Cure” is a fre-

quent rallying cry in the names oforganizations and fundraisingevents. At Dana-Farber and othercancer centers, health care providers

As our knowledge of cancer grows,our vocabulary for dealing with thedisease grows with it.


75

1974 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004

70

65

60

55

50

45

Thirty years ago, half of cancer patientssurvived five years or more; today, therate is more than two-thirds.

“People tend to forget where we were and where we are now – our progress isincremental, but our progress is real.” — Len Lichtenfeld, MD

will tell you that being part of thismission is what brings them to workevery day.After all, the reasoning goes, sci-

ence and technology have defeatedpolio and smallpox, sent people tothe moon, unlocked the code of thehuman genome. Why should bio-medicine not eradicate the scourgeof cancer?But with increasing knowledge of

cancer’s many faces and its abilityto outwit medical attacks, the defi-nition of the term “cure” growsmore ambiguous. As researchersdelve ever deeper into the geneticjungle of the cancer cell, their visionof an outright cure – especially asingle, cancer-eliminating solution –is giving way to other “c” words,such as conquer, control, and mak-ing cancer a chronic disease: a suc-cessful long-term campaign ratherthan a knockout blow.“Cure is a word that I don’t

use a great deal; it is promisingsomething that may or may not bepossible,” says Robert J. Mayer,MD, a senior cancer researcher atDana-Farber and physician atDana-Farber/Brigham and Women’sCancer Center. “Instead I say topatients, ‘You will be alive and well,and in 20 years we’ll look back atthis and have a chuckle.’”Certainly, some cancers can be

cured today, and others will be inthe future. Cancer is an umbrellaterm for several hundred differentdiseases all caused by damagedDNA that spurs cells to growuncontrollably, invade tissues andorgans, and spread menacingly todistant parts of the body. Furthercomplicating matters, cancer cells

aren’t derailed by a lone defect, butoften have an array of abnormali-ties that enable them to survive thebody’s cellular self-destruct mecha-nisms. They are also quite adept atevading even the most powerful andtoxic cancer drugs. Few scientiststoday envision one all-powerful keythat would solve the puzzle.

“Will we have the magic bulletthat will cure all cancer? Theanswer is no, but we will increas-ingly be able to keep this diseaseunder control – people will live along time with it,” says LenLichtenfeld, MD, deputy chiefmedical officer for the ACS.“People tend to forget where wewere and where we are now – ourprogress is incremental, but ourprogress is real.”

Realistic goalsExcept for surgical removal and

occasionally successful radiationtherapy, no reliably effective cancertreatments existed until the late1940s, when DFCI founder SidneyFarber, MD, achieved the first(though initially very temporary)remissions in childhood leukemiawith the forerunners of today’schemotherapy drugs. The opening ofthe chemotherapy era inspired asurge of optimism and successfullobbying for government funding. In1957, an official of the NationalCancer Institute declared: “The nextstep – the complete cure – is almostsure to follow.”Farber himself was bullish, believ-

ing that a cure was on the horizon,“lacking only the will and the kindof money and comprehensive plan-ning that went into putting a man on

the moon,” as he was quoted in aNewYork Times full-page ad callingon then-President Nixon to wage anall-out “War on Cancer.” Intenselobbying by Farber and other physi-cians and by citizen activists led toNixon’s 1971 National Cancer Act,which provided record-high fundingfor cancer research but at the sametime raised unrealistic expectations.Nearly 30 years later, in 1998,

the ACS issued a more modestchallenge to the cancer community:Between 1992 and 2015, it hopedto see “a 50 percent reduction inage-adjusted cancer mortality rates;a 25 percent reduction in age-adjusted cancer incidence rates; anda measurable improvement in quali-ty of life (physical, psychological,social, and spiritual) from the timeof diagnosis and for the balance oflife of all cancer survivors.”In 2007, the ACS reported that

despite progress, it was unlikelythose goals would be achieved with-out “substantial breakthroughs” inearly detection or treatment. As of2004, cancer incidence rates haddropped 10.2 percent since 1992 –less than half of what would be

Year of diagnosis

A rise in average cancer survival rates

Percentsurviving

Source: National Cancer Institute


Even though they are not “cured,” many peopletoday are living quite well for extended periodswith even the most deadly forms of cancer. Here

are reflections from three patients of Robert J. Mayer,MD, on the subject.

“When I was first diagnosed, the doctors said mydisease was treatable, but we just don’t have a cure now.It was hard to hear,” says Michelle Grant-Epstein,a 52-year-old mother of three from Framingham, Mass.The advanced colon cancer diagnosed in 2005 hadspread to one of her ovaries, requiring extensive surgeryand chemotherapy, which is continuing in the wakeof a recurrence.As Grant-Epstein thinks of it, she is “cohabitating”

with her cancer, “and as long as I’ve got the upper hand,that’s OK.” The disease doesn’t prevent her from being a“fully functional adult,” she says – exercising at home,spending time with her family and friends, and workingpart-time at a local library.“Do I wish for a cure? Absolutely!” she adds. “But I

know that it’s complicated and each cancer is different.For now, I’m grateful for the drugs that are controllingmy cancer, and I hope they’re still working.”

Edward Bromfield, MD, a neurologist at Brighamand Women’s Hospital, was diagnosed in 2006 with pan-creatic cancer, an aggressive disease rarely detected earlyenough for potentially curative surgery. A series ofchemotherapy regimens has kept him feeling relativelywell and active enough to continue playing basketballregularly with his group of longtime friends.“I think the term ‘cure’ still has meaning,” says

Three Survivors

the 57-year old Bromfield. “It’s not for me, in my situa-tion, but I know a number of people who could be con-sidered cured – they have no recurrence of cancer aftersome substantial number of years.”For himself and many others, Bromfield uses the

words “successful treatment.” This means, he says,“successful in the sense that you can live your lifeas normally as possible and you don’t have the sensethat things are getting worse.”

When Mieko Komogata’s mother was diagnosedwith stomach cancer 25 years ago in Japan, doctorstold her family but purposely hid the diagnosisfrom the patient. She had successful surgery andto this day thinks it was for an ulcer.Mieko herself, a software developer who lives in

Stow, Mass., developed a stealthy form of stomachcancer that took years to diagnose, and in 2002 sur-geons removed her entire stomach. She was then treat-ed with chemotherapy and radiation.She has been free of cancer since then, and the

48-year-old Komogata says she’s been told that herchances of having a recurrence are becoming smalleras she continues to have normal tests.“Still, the chances of recurrence are not zero – there

is no single cure,” she says. “But I feel healthy andhappy. Doctors are making progress, and I am veryhopeful that risks of cancer can be reduced. I wantpeople to know that cancer is not a death sentence.”

necessary to meet the 25 percentincidence reduction goal by 2015.Cancer death rates also declined

between 1992 and 2004, but at apace that is estimated to reducedeaths by about 38 percent by2015, rather than the hoped-for

reduction of 50 percent.Dana-Farber has set a goal “of

conquering at least one major formof cancer within a decade.” Thegoal, explains President Edward J.Benz Jr., MD, is not necessarily acomplete cure.

“Many people think that cancer islike polio, that there will be a pictureof a vial of something in the newspa-per and [the disease] is gone,” hesays. “That’s what we’d like cancerto be – something our grandchildrenwon’t even remember.”

Mieko Komogata hasn’t slowed down in the wake ofserious stomach cancer, for which she was treated in 2002.


However, says Benz, “The realityis that most cancers will be man-aged rather than eliminated, andpeople will be able to live withthem and deal with them. Exceptfor some infectious diseases thatwe cure with antibiotics, there arealmost no diseases where we takethem away and they never comeback again.”

Redefining progressEven if a cure has been elusive,

new chemotherapy combinations,along with improved surgery andradiation, have brought better out-comes. Cancer has become muchbetter understood – especially in thepast decade, as its genetic rootshave been uncovered. Advances indiagnosis, detection, populationscreening, and the advent of target-ed treatments like the drug Gleevecin the past decade are all making a

difference. In the early 1970s, halfof patients with cancer lived fiveyears or more; today it is more thantwo-thirds.“I’ve had patients whom I’ve

treated for 20 years – including twowomen with metastatic breast can-cer – and it’s extremely gratifying,”Mayer observes. “Many of themare not cured, but they are livingtheir lives in a full and robust man-ner. We now have more effectivetreatments that last a longer periodof time.”To be sure, some types of cancer

can be treated today with a veryhigh probability that the patientwill be alive five years later andprobably far beyond. Childhoodleukemias, thanks to the pioneeringwork of Farber and others, havegone from being universally lethala few decades ago to curable in80 percent to 90 percent of cases.

Testicular cancer and Hodgkin lym-phoma have high cure rates, too.In fact, Mayer points out, a patientwith almost any cancer that iscaught and treated early, includingpotentially deadly types likemelanoma, pancreatic, ovarian,lung, breast, and colon cancer, hasvery good odds of long survival.A major challenge, however, is thatsome of the most lethal cancers,such as ovarian and pancreatic, areextremely difficult to detect whenthey can be effectively treated.At this point in the history of

cancer and its treatment, no singleyardstick of success, like the term“cure,” accurately reflects what med-icine can do or hopes to do in theforeseeable future.To measure progress only in

terms of eradicating cancer missesthe point, adds Mayer. “It’s likesaying the only way you can score

The dramatic risein childhood cancercure rates, fromvirtually zero in1950 to around80 percent today,is one of the majorsuccess stories incancer treatment.


a run in baseball is by hitting ahome run.”

The language of the cureEven if the word “cure” is over-

used, there are times and placeswhen it serves an important pur-pose, says K. Vish Viswanath, PhD,a specialist in health communica-tion at Dana-Farber and the HarvardSchool of Public Health.“My argument is that we cannot

use just one message for the publicas a whole,” says Viswanath. Hesays there are a number of different“publics,” each with different needs.Among them: scientists and healthproviders, who speak in cautiousand precise terms; people whoare “engaged” with cancer – currentpatients and families, and longer-term survivors; and the “generalpublic,” which doesn’t spend a lotof time thinking about cancer.“And then there is the advocacy

community,” Viswanath adds. “Weknow that the way you mobilizepeople around a common cause isto frame it in a way that stimulatesoutrage.” Viewed in this light, hesays, calling an event a “race forthe cure” is really a metaphor – amotivational strategy rather thana concrete goal.Similarly, says Viswanath, there

is a reason for the common militarymetaphors such as a “war oncancer” fought with “smart bombs”and vaccines that rally “armies”of immune cells to attack tumors.“Pithy phrases like these,” headmits, “are more likely to resonate

than saying, ‘Our goal is to under-stand the molecular basis of cancerand target those gene modificationsto stop cell proliferation.’”No amount of debate or skepti-

cism about a cure, however, willslow the pace of research aimedat blocking the fundamentalprocesses of cancer. Equally impor-tant, cancer specialists and organi-zations emphasize that much morecan be done with the knowledge

already gained. For example, it’sestimated that about half the cancerdeaths in the United States arerelated to tobacco use, physicalinactivity, obesity/being overweight,and nutrition. It is obvious that can-cer prevented is even better thancancer cured.Five years ago, a federal study

projected that 60,000 deaths and100,000 new cases of cancer couldbe prevented annually by 2015,using current early detection andprevention measures.

Looking ahead, oncologist Mayerpoints to inroads being made withnewer targeted treatments likeGleevec®, Tarceva®, and Herceptin®

that are tailored to the genetic traitsof specific patients’ tumors. “It’sbeen a remarkable decade – amongother things, we’ve learned thatone size doesn’t fit all in cancertreatment,” he says. “We’re seeingsurvival improvements of 5 percenthere, 10 percent there ... this is not

a day-and-night difference, butthis is progress.”Cancer may not be totally elimi-

nated any time soon – or ever.Advances are generally incremen-tal, and victories will likely comeone cancer type – or subtype – ata time. But there is no denyingthat more lives are being savedtoday, and the quality of thoselives is better than in the past. Ifthis is not “a cure” in the strictsense of the word, it is surely thenext best thing.

How the word “cure” is useddepends on the specific audience,says Vish Viswanath, a healthcommunication specialist.

“It’s like saying the only way you can score a run inbaseball is by hitting a home run.” — Robert J. Mayer, MD


downsUps&

Taking the steps to recovery

By Saul Wisnia

Julie Silver is focusedon ”healing optimally“after treatment.

Looking back, Julie Silver, MD, realized that one of thedefining moments of her breast cancer treatment waswhen her 4-year-old daughter complained about her

mommy “just sitting around.” As a rehabilitation physicianwho prided herself on being active with her three youngkids, Silver tried to keep up her strength during treatment,but sometimes it just wasn’t possible. She had constantpain in her hands and feet that made the easiest tasksarduous and old joys like running around the backyardnext-to-impossible.One friend noticed a pattern. She wouldn’t hear from Silver

until eight days after her biweekly chemotherapy infusions atDana-Farber, when her e-mails or calls would suddenly comein a torrent. A few days later, when another chemo doseloomed, she’d grow silent again.

“People feel that healing is a fairly smooth process – yougo from having cancer to feeling better and better, and thenyou’re done – but it’s not that simple,” explains Silver, whowas 38 when first diagnosed in 2003 and is now in remission.(Silver leads patient workshops on survivorship at Dana-Farber; see story on page 14.) “Setbacks and plateaus are partof the process. Usually you go to a doctor who gives youtreatments that make you feel better, but with cancer you mayfeel worse before you can get better.“And it’s not always during the treatment itself that you feel

your worst,” she adds. Patients who are getting chemotherapyevery second or third week, for instance, say they often feelsicker during their “off ” weeks as their bodies try to recoverfrom the physical onslaught of drugs. Since they are usuallyhome during these periods, they don’t have the constant reas-surance of clinicians and support staff, sometimes resulting instress for them and their families. And while some side effectsassociated with cancer therapy such as hair loss, nausea, andlymphedema (arm or hand swelling) are well known, there aremany other emotional and physical “ups and downs” experi-enced by both adults and children during and after treatments.Whether it’s depression, dramatic mood swings, or fatigue

that can make even simple conversations seem daunting,patients and families often must deal with these less publi-cized challenges along with the rest.“I went to the mall the other day with some friends and had

a great time, but while we were driving home I just startedcrying,” says Von Marie Rosario, a 19-year-old being treated


Julie Silver, MD, has developed a holistic approach to healing thatshe shares with others through workshops at Dana-Farber and herbook, After Cancer Treatment: Heal Faster, Better, Stronger. Among

her recommendations:

• Employ “super healing energy”:Work at optimizing yoursleep, being as active as you can physically, and eating ahealthy diet.

• Make “fatigue” an agenda item with your oncologist:How you’re sleeping at night and whether you’re depressed orhave sleep apnea are important factors in your recovery. Anemia,hormonal fluctuations, and/or other treatable conditions may becontributing to your fatigue.

• Avoid “emotional ambushes”: If you hear something, like newsabout a public figure whose cancer treatment isn’t going well,recognize that it’s not about you; your diagnosis has not changed.

• Share details as you see fit: Individuals don’t owe it to anybodyto talk about their diagnosis. Do what’s comfortable for you.

Getting through each day

Holcombe Grier (left) and LewisSilverman help children enjoy lifearound treatments.

for Hodgkin lymphoma in Dana-Farber’s Jimmy Fund Clinic. Sheattributes her frequent mood swingsto the steroids she takes every otherday in conjunction with her weeklychemotherapy. “I get easily angryand easily sad, and it’s hard for myfriends to understand it.”Family members who do under-

stand can also find this emotionalroller coaster taxing. “It affectseverybody in the house,” says KarenBernard, whose 16-year-old daugh-ter, Kelley, is being treated in theJimmy Fund Clinic for acute lym-phocytic leukemia (ALL). “She’sa friendly, warm-hearted person,so when she starts lashing outduring her big steroid week, itreally stands out.”Fatigue can be another problem.

Rosario took a leave from her job ata clothing store when she startedtreatment in April, and even goingback to a few shifts a week has beendifficult. Vinnie Corsaro can relate;a 56-year-old carpenter and teacher,he was forced to stop work last year

during treatment at DFCI for ton-sil and lymph node cancer, andstill has ringing in his ears andnumbness in his feet months afterfinishing chemotherapy.For Corsaro, however, the toughest

challenge has been the impact onhis taste buds – another side effecthe hopes will disappear in a year ortwo. “Most things don’t taste verygood, and I don’t enjoy cooking any-more,” he says. “Sometimes the curefeels worse than the disease.”

Seeking controlDana-Farber is taking steps to

address such feelings. Each newpatient and his or her familyhas access to a clinical socialworker, either through the CareCoordination Department of theDana-Farber/Brigham and Women’sCancer Center (DF/BWCC) for adultpatients or the Jimmy Fund Clinic’sPediatric Psychosocial Unit, run inconjunction with Children’s HospitalBoston. Beyond psychosocial assess-ments and interventions, social

workers tackle both emotional andlogistical concerns.In addition to meeting individually

with patients, DF/BWCC psychologistKaren Fasciano, PsyD, and socialworker Mary Ann Holcombe, LICSW,lead group sessions in which theyteach emotional coping skills such asstress management strategies to alternegative thoughts, and behaviors tochange one’s mood. For example, theyencourage patients to “schedule”worry time so they don’t let fearsoverwhelm them, and to organize timeor activities with loved ones that arefree from discussions about cancer.Another teaching device they use

is cognitive restructuring. “We lis-ten to peoples’ thoughts and workwith them to develop more adaptiveways of thinking about the same sit-uation,” Fasciano explains. “Insteadof saying, ‘Cancer has taken overmy life,’ we encourage them toreplace it with something like,‘Cancer has taken over part of mylife, but I’m not going to let it con-trol all of my life.’”Even when patients are too young

to understand the implications of adiagnosis, the same fears are often

around the challenges. When it’sclinically safe, physicians will occa-sionally put off starting a new seriesof chemotherapy drugs or steroidsby a few days so a patient can enjoya birthday party or other majorevent. One woman remembers herlate husband working with hisdoctor to rearrange a chemo treat-ment around an upcoming BruceSpringsteen concert.“When I’m on my five-day dose

of steroids, I’m claustrophobic, can’tstand messes, and am generally not apleasant person to be around,” saysKelley Bernard, who had to give updancing and most of her sophomoreyear of high school during her ALLtreatment. “I’ve just learned to makethe most of my ‘good’ weeks andhang out with my friends or go tothe gym as much as I can then. If Igive people my look, they know Ineed my space.”While the cancer treatment itself

has been grueling for Bernard andher family, she and others agree thatthe emotional, physical, and logisti-cal challenges during and between ithave often been just as taxing. Nowthey’re eager for a return to their oldroutines – whether that’s dancing,enjoying the taste of their gourmetdinners, or simply chasing their kidsaround the backyard.


Kelley Bernard looks forward to when she can join her mother (rear) on thedance floor again.

there. In more than 25 years as apediatric oncologist at Dana-Farber,Holcombe Grier, MD, has learnedthe importance of respecting youngpatients’ intellects and easing theiranxiety by always including them inconversations and decision-makingabout their care. And in the case ofteenage patients, asking parents toleave the room so he can discussmore private matters like drug useand sex can both calm patients andwin their trust and respect.“At almost any age, except for the

youngest babies, there is a desire toexert some control over your envi-ronment,” Grier says. “When [med-ical] residents are doing rounds withme and ask a child, ‘Do you mindif I listen to your chest?’ I correctthem.You’re not giving the kid achoice; you’re going to listen to itno matter what. You need to bethoughtful and say, ‘I have to listento your chest. Do you want me todo it here, or do you want to standover by Mommy?’”

Sharing insightsGrier’s colleague Lewis Silver-

man, MD, director of the JimmyFund Clinic, says that clinic person-nel are always working to betterunderstand the side effects youngpatients face from chemotherapy andsteroid treatment, and alter dosageswhen possible. Dana-Farber is part-nering with seven other hospitals toconduct a series of clinical trialsinvolving ALL, the most commonchildhood cancer, with 5,200 newcases annually (most of them chil-dren). In the current trial, hundredsof pediatric patients ages 2 to 18 andtheir parents are being surveyed onthe impact of the chemotherapy drugasparaginase on their quality of life.

“There is something we’ve identi-

fied as the ‘asparaginase blues,’where the many patients who takethis drug for the typical 30-weekperiod lose their energy andappetite,” explains Silverman. “Wewant to understand how these symp-toms change over time, and whetheror not different types of asparagi-nase may have different results.”In another effort beginning this

fall, Dana-Farber will allow adultpatients to log on to the secure“Patient Gateway” Web site andreport symptoms and side effectsthey are experiencing while on dif-ferent drugs. “Our concern is thatpatients who come into the hospitalevery three weeks may not remem-ber how they felt each week inbetween,” says Saul N. Weingart,MD, the Institute’s vice president forpatient safety. “If they can tracksymptoms at home and report themeach week when prompted, we hopeit will give them a sense of powerand control over their disease andallow us to better help them. We stillwant patients to contact us directlywith any serious symptoms, but weenvision building a ‘self-help’ sec-tion and creating opportunities forpatients to interact electronicallywith a doctor or nurse practitioner.”In the meantime, patients and cli-

nicians do what they can to work


Bruce Johnson leads a team of researchers rolling backgenetic mysteries of lung cancer.


For a drug that became thefirst of a new generation oflung cancer treatments,

Iressa® started out as one of themost puzzling medicines in history.When given to patients with non-

small cell lung cancer – or NSCLC,by far the most common form ofthe disease – the drug generallydidn’t provide much benefit, except

in a small minority of cases wherethe results were spectacular.Doctors couldn’t predict whichpatients would be among the luckyfew. Some experts argued the drugshouldn’t even be approved for lungcancer, since it worked so sporadi-cally, but the successes were toocompelling to ignore.Researchers at Dana-Farber and

their colleagues began to piece to-gether evidence earlier this decadethat Iressa’s rare but dramaticeffects were tied to the geneticmakeup of NSCLC tumors.One hint came from the experi-

ence of treating patients: Doctorshad noticed that Iressa (chemicalname: gefitinib) has a higher suc-cess rate in Japanese patients thanAmericans. When Dana-Farber’sMatthew Meyerson, MD, PhD, andWilliam Sellers, MD, scanned a col-

lection of NSCLC tumors for mal-functioning, or mutated, genes, theyfound that the gene EGFR (whichstands for “epidermal growth factorreceptor”) was faulty in 15 Japanesepatients, but in only one from theUnited States. Research had shownthat Iressa acts directly against theprotein made from EGFR.(Meyerson also holds an appoint-

ment at theBroad Instituteof MIT andHarvard; Sel-lers is nowbased at Nov-artis, a phar-maceuticalcompany.)A second

hint came fromwork by Dana-Farber’s BruceJohnson, MD,

and Pasi Jänne, MD, PhD. Theyfound that tumor tissue from awoman with cancer that hadspread to the lining around herlungs – a condition called adenocar-cinoma – was very responsive toIressa when tested in a laboratorydish. When the adenocarcinoma’sDNA was analyzed, it was foundto have the same EGFR mutationthat Meyerson and Sellers’ grouphad found.“We knew that EGFR mutations

are more frequent in women, inJapanese, and in people with adeno-carcinoma,” says Johnson, directorof Dana-Farber’s Lowe Center forThoracic Oncology. “These are thesame groups that are most likely toexperience tumor shrinkage whentreated with Iressa.”To test whether Iressa indeed

works best for patients with EGFR

Lung DistanceBy Robert Levy

Extending the reach oflung cancer treatment


therapy’ [aimed at a particular mis-behaving gene or set of genes]could be effective against a form oflung cancer,” says Johnson. And itbecame the model by which othergene-focused treatments forNSCLC could be identified, tested,and approved for patient use.This summer, Lowe Center

researchers and physicians opened agenotyping service where NSCLCpatients at Dana-Farber/Brighamand Women’s Cancer Center can

have their tumors scanned for eightgene abnormalities associated withthe disease. The information willhelp investigators gauge the preva-lence of such mutations and theeffectiveness of various targetedtherapies. The service, establishedwith financial support from theFriends of Dana-Farber CancerInstitute, provides a foundation forthe kind of personalized medicinethat Bruce Johnson and others envi-sion: a place where lung cancer

Promise in the air for mesothelioma treatments

Efforts to remove asbestos from thousands ofbuildings across the United States in the past30 years may have given people the impression

that mesothelioma – an often fatal form of lung cancerlinked to asbestos exposure – is increasingly rare. Infact, because symptoms of the disease usually don’tappear for 30 to 50 years after exposure, expertspredict the annual number of new diagnoses willcontinue to climb until 2015.Research at the molecular level and the adoption

of new treatment approaches are raising hopes ofimprovements in doctors’ ability to treat the disease.Scientists at both Dana-Farber and Brigham and

Women’s Hospital (BWH) are conducting mesothe-lioma research along a range of fronts: from thedevelopment of new surgical approaches to the useof tiny particles that piggyback medication directlyto tumors. These efforts benefit from BWH’s bank ofmesothelioma tumor tissue for study, the largest suchbank in the world.“Mesothelioma provides a prime example of the kind

of progress that can be made when two institutions sharea commitment to improving treatments for a disease andtheir staffs work as a team,” says David Sugarbaker, MD,director of the International Mesothelioma Program andchief of the Division of Thoracic Surgery at BrighamandWomen’s Hospital, as well as a staff surgeon atDana-Farber/Brigham andWomen’s Cancer Center.

Among the most promising areas of researchare these:

• Working with software engineers, Dana-Farber andBWH investigators have demonstrated that advanced DNAsequencing systems can identify the unique set of abnor-malities in mesothelioma tumors. The finding suggests apractical way of reading tumors’ genetic signatures andusing that information to guide therapy.

• Clinical trials are examining a surgical technique thatinvolves applying chemotherapy agents directly to tissuewhere mesothelioma tumors are embedded. Such “intracav-itary chemotherapy” will, it is hoped, reduce chances thattumors will recur after removal. Early results indicate thatpatients enrolled in the trials live longer than those receiv-ing standard chemotherapy.

• Investigators are exploring whether drugs known asM-tor inhibitors, which block a key protein, can increasethe potency of conventional chemotherapy agents.

• Scientists are investigating whether lab-made nanoparti-cles a fraction the size of human cells can be used aschemotherapy delivery vehicles. The nanoparticles wouldbe hitched to chemotherapy agents and equipped with anti-bodies that draw them to the surface of cancer cells. Spreadin a salve or gel on tissues at the surgical site, the chemo-carrying particles could help eliminate any remainingtumor cells.

mutations, the researchers analyzedtumor samples from five patientswhose tumors had responded to thedrug and four whose tumors hadn’t.All of the responders had EGFRmutations; the other four did not.The publication of this work by

the Dana-Farber team in 2004 – andthe simultaneous publication of arelated study by other investigators– propelled lung cancer treatmentinto the genomic age. “It was thefirst demonstration that a ‘targeted

Lung cancer remains the leading cause of cancer death in men and women in theUnited States. This year, the disease will claim the lives of 161,840 Americans.


patients can have their tumors“typed” – much as bacterialinfections are categorized by thekind of bacteria involved – andtreated accordingly.

Formidable foeThe 2004 breakthrough could

not have come against a moreimplacable opponent. Despitedeclines in cigarette smoking andother forms of tobacco use, lungcancer remains the leading causeof cancer death in men and womenin the United States. This year, thedisease will claim the lives of161,840 Americans, according tothe American Cancer Society –more than breast, colorectal, andprostate cancers combined. Notonly are cure rates for lung cancerlower than for most other majorforms of cancer, they have barelybudged in recent decades. Lungcancer patients have only a15 percent chance, on average,of being alive five years aftertheir initial diagnosis.Against this backdrop, it’s impor-

tant to appreciate the significance,and the limitations, of the advanceinvolving Iressa. (Iressa itself is notcurrently approved for new patientswith lung cancer in the UnitedStates; doctors generally prescribethe alternative drug Tarceva®.) Lungcancer is classified as either small-cell or non-small cell, accountingfor 13 percent and 87 percent of allcases, respectively. Of the non-small cell group, only about 12percent have an EGFR mutationthat makes them candidates fortreatment with Tarceva. (AmongJapanese and other Asian peoples,the prevalence of EGFR mutationsin patients with NSCLC is consid-

Kwok-kin Wong (left) and Pasi Jänne work to apply lessons from the lab toclinical settings.

erably higher – as much as 40 or 50percent.) Twelve percent may soundrelatively small, but with 187,000people diagnosed annually in theU.S. with NSCLC, a 12 percent por-tion works out to 22,440 patientswho potentially can benefit fromIressa or Tarceva each year.Also to be considered are the

gains in length and quality of lifeassociated with Iressa or Tarceva.

For most patients with NSCLC,conventional chemotherapy providesan additional four to six months ofsurvival over what they would havewithout treatment. Patients whorespond to Iressa or Tarceva, bycontrast, can expect another year ormore. (Like most cancer drugs,Iressa and Tarceva lose their powerover time as tumor cells becomeresistant to them.) And, because


At the Lowe Center, aphilosophy of empathy

To put oneself in the place of a lung cancerpatient and his or her family is more than amatter of empathy. At the Lowe Center for

Thoracic Oncology at Dana-Farber/Brigham andWomen’s Cancer Center (DF/BWCC), it forms thephilosophy of care.The center’s clinicians work on the principle that

lung cancer leaves virtually no aspect of people’slives untouched, so patient services need to be bothbroad-based and broad-spirited. The care team includesphysicians, nurses and nurse practitioners, painspecialists, nutritionists, social workers, and mentalhealth professionals.“We try to be attuned to the whole family dynamic,”

says nurse practitioner Pamela Calarese, RN, MS, CS.“If the patient has children, for example, we want to besure his or her emotional needs are addressed. We get toknow the ‘significant other’ – a husband, wife, or friend– who accompanies a patient to appointments to seehow we can help that person as well. Our social worker,Bryan Harter [LCSW], gets involved as soon as treat-ment begins, to coordinate services for the family.”Particular attention is paid to patients’ psychological

issues. “Many times, we’re able to anticipate whatthey’re going to go through emotionally,” Calareseremarks. “With smokers, for example, there’s often asense of guilt about having brought the disease onthemselves, and feelings of depression about theirfuture. People who never smoked, on the other hand,feel baffled: ‘How did this happen to me?’Wedon’t hesitate to refer people experiencing thesekind of difficulties to a staff psychologist, psychiatrist,or social worker.”Underlying this approach is a determination that

patients not feel alone in dealing with their disease. It’s

reflected in the appointment of a triage nurse, CatherineHooper, RN, OCN, whom patients can call with ques-tions or concerns that otherwise might require a tripto the clinic.“Lung cancer is a tough disease,” Calarese comments.

“If I had a family member who had it, I’d want to besure they’d have someone to talk to. That’s what we tryto provide.”Services cover a spectrum of areas, from medical

treatments to quality of life issues. Pain and symptommanagement is a prime focus, with specialists fromDF/BWCC’s Pain and Palliative Care team availablewhen needed. Nutritionists offer guidance in eating aswell as possible, even when the rigors of treatment makefood unappetizing. Religious clergy attend to spiritualconcerns, and a support group is available to helppatients and family members cope with the demandson their lives.As new treatments help patients live longer, the need

for such services is increasing. “There’s a level of com-mitment here that we truly feel present for our patients,”Calarese says. “We talk about their work, what theyenjoy, and we do it with humor and a lot of love.”

Catherine Hooper can often save patients a trip to theclinic by answering their questions by phone.

vival time – no mean feat in a fieldwhere progress was frustratinglyslow for many years.

Out of hibernationIn some respects, lung cancer is

a relative latecomer to targetedtherapy. Breast cancer treatment is

increasingly personalized, withtreatment regimens geared to spe-cific gene mutations in patients’tumors. Lung cancer research, bycontrast, has long suffered from thedifficulty of obtaining tissue forstudy and from a reputation as anarea with few good scientific leads.

they concentrate their effects oncancer cells, rather than a broadrange of cells, Iressa and Tarcevagenerally produce fewer side effectsthan standard treatments do.To an outsider, such gains might

seem modest, but, as Johnson pointsout, it represents a doubling of sur-


Matthew Meyerson leads efforts to probe lung tumors for abnormal geneslinked to cancer.

The discovery of NSCLC’smolecular vulnerability has giventhe field fresh energy, by essential-ly mapping a route toward thedevelopment of new gene-orientedtherapies. At Dana-Farber, Johnsonhas assembled a team of scientiststo carry the process from start tofinish. Meyerson is leading theeffort to scan tumor tissue forpotential cancer genes; Kwok-kinWong, MD, PhD, is conductingtests in laboratory cell cultures andmice to determine if abnormalitiesin those genes are indeed linked tocancer; and Pasi Jänne is studyingthe effectiveness of therapies forsuch target genes in patients.The goal, as Johnson puts it, is to

“chip away at the problem of non-small cell lung cancer” by findingand defeating additional geneslinked to the disease. Chances are,each of these genes will be respon-sible for only a small percentage ofNSCLC cases – perhaps just 2 per-cent or 3 percent – but cumulativelythey may affect a quarter of allpatients with the disease.“We want to make it routine to

test patients’ tumors for knownmutations, so their treatment can betailored to their specific abnormali-ties,” Johnson says. Some of thosetherapies may already be “on theshelf ” – used for other diseases andtherefore readily available.Dana-Farber researchers are cur-

rently on the trail of severalNSCLC-linked genetic abnormali-ties – instances of misspellings of agene’s chemical code, or caseswhere a gene is overcopied or stuckin the wrong portion of a chromo-some. In some instances, thesesame abnormalities are found in

other cancers for which drugs areavailable, raising the possibility thatthey’ll work in certain non-smallcell lung tumors as well.Meyerson is co-leader of a group

that has sequenced more than 600genes in almost 200 lung cancersknown as adenocarcinomas, andhas discovered more than 15 signif-icant new mutated genes. “In thisone survey, we have more than dou-bled the number of known geneswhose mutation can lead to lungcancer,” Meyerson says.Dana-Farber scientists also have

been the first to show how NSCLCcells gain the ability to shrug offIressa or Tarceva and resume theirrampant growth. In one study,Jänne and colleagues found thatafter a year of Iressa or Tarceva use,50 percent of patients acquire an

additional mutation, and 20 percenthave an overcopying, or “amplifica-tion,” of genes, which loosens thedrugs’ grip on their runaway growth.“We’re at work on a second genera-tion of EGFR inhibitors that circum-vent the problem of resistance,”Jänne says.“Today, we can identify the genes

driving tumor growth in a substantialportion of non-small cell lung cancerpatients,” observes Wong. “The firstchallenge is to devise successfultreatments keyed to those genes. Theother is to find additional geneticculprits.” Wong admits that thesemutations already linked to the dis-ease may be the easiest to find –“low hanging fruit,” as they’re called– and that additional ones may bemore elusive. But, he adds, “There isa lot of low-hanging fruit.”

“We want to make it routine to test patients’ tumors for known mutations, so theirtreatment can be tailored to their specific abnormalities.” — Bruce Johnson, MD


When breast cancer sur-vivor Martha Haywardgives talks at other

organizations about Dana-Farber’spatient-centered approach to care,her audience is often surprisedwhen she steps up to the micro-phone. “They are not used to hear-ing from an actual patient,” explainsHayward. “It’s not until I go else-where that I realize how unusualour style is here.”Hayward is a member of the

Adult Patient and Family AdvisoryCouncil (PFAC) at Dana-Farber/Brigham and Women’s CancerCenter (DF/BWCC), which, alongwith the pediatric PFAC, is at theheart of the Institute’s patient-centered philosophy. For the last10 years, the adult council hasaddressed the care provided throughDF/BWCC, while its pediatriccounterpart, founded in 1999,

focuses on patients of Dana-Farber/Children’s Hospital Cancer Care.Together, the councils give

patients and families the opportu-nity to be leaders and educators,spreading the message of patient-and family-centered care locallyand internationally, and teachingstaff members at all three partnerhospitals what it means to be apatient. Advice from these groupsis sought on nearly every importantmatter concerning patients andfamilies, from shortening the timespent waiting to be seen by a clini-cian to helping plan clinics beyondthe Longwood medical area.

Patients as teachersIn a traditional picture of health

care, clinicians are on one teamand patients on the other. Thepatients are physically and emo-tionally vulnerable, and doctors,

nurses, and other providers have theknowledge and skills to make thembetter. Dana-Farber works from adifferent paradigm, in which bothsides have wisdom to impart.Patients are considered experts inbeing patients, and their perspec-tives make the organization better.“When I describe our Patient andFamily Advisory Councils to col-leagues outside Dana-Farber,” saysJanet Porter, PhD, DFCI’s chiefoperating officer, “They ask, ‘Whatdo you call the patients and fami-lies who do this work?’And I say,‘I call them teachers.’ They teachme what it means to be a cancerpatient. As leaders, we have to behumble. Who am I to say what acancer patient needs?”Currently, advisory council mem-

bers serve on more than 80 com-mittees and project planninggroups, making “Let’s ask the

Two-time cancer survivorKari Dudley (right) isorganizing a speakers’bureau to manage speak-ing requests for survivorssuch as Martha Hayward.

Leading the wayCouncil members spread themessage of patient-centered careBy Christine Cleary


council” a common refrain amongstaffers planning clinical programs.“To call them ‘advisors’ is not

strong enough,” points out CarolynHayes, PhD, RN, director of theInstitute’s Shapiro Center forPatients and Families. “They are

not on the sidelines offering theiropinions. They often work so hardwe have to remind ourselves thatthey are volunteers, not employees.

“I consider myself to be patient-centered,” adds Hayes, “yet thecouncil members always teach mesomething I didn’t know.”Increasingly, health care leaders

beyond Dana-Farber are recognizingthe importance of this patient-centered approach. Dana-Farber wasrecently named the second annual

recipient of a Health Care Excel-lenceAward by Blue Cross BlueShield of Massachusetts, cited as aleader in engaging and empoweringpatients in every aspect of care. (Seestory on page 3.)“Visitors are astonished that we

include patients and families inmeetings where we talk about sen-sitive subjects such as medicalerrors, and seek their help inenhancing our patient safety pro-grams,” Porter says. She often citesher surprise and delight that thesearch committee for her positionas chief operating officer includeda patient, who fired tough questionsduring the interview process.“After a recent speech I gave

about patient involvement in the

design of our newYawkey Centerfor Cancer Care,” she recalls,“someone asked, ‘Isn’t it exhaust-ing to ask patients and familiesevery time you do something?’ Isaid, ‘No, it’s easier, because thenyou are more likely to get it right.’”

Ambassadors for careCouncil members are frequently

invited to speak at health careorganizations and conferences inNew England and beyond aboutsuch topics as teen and young adultcancer survivorship, patient safety,and how to create a patient-cen-tered model of care. They teachstaff, other patients, and otherorganizations, and their engage-ments are so frequent that councilmember Kari Dudley is formalizing

“They teach me what it means to be a cancer patient.” — Janet Porter, PhD

Andrew MacKinlay and his mom, Cyndi, give talks about what it’s like to bea childhood cancer survivor.

Caroline and Mike Rider find timeto serve on the pediatric councildespite their busy family life.


a speakers’ bureau to respond torequests, seek new opportunities,and offer training to speakers.“We invited two council members

to speak to our board of directors,and we were impressed by the factthat patients and families really dowork in partnership with hospitalleaders in every aspect of care,”says Julie Rosen, executive directorof the Kenneth B. Schwartz Center,an organization that strengthens therelationship between patients andcaregivers, and helps caregiversprovide compassionate health care.Recently, Martha Hayward trav-

eled to Irkutsk, Russia, with YelenaWetherill, PhD, a Dana-Farberbreast cancer researcher, to helpteach women the value of earlydetection. Pediatric council co-chair Eric Rodriguez is a popularspeaker within and outside Dana-Farber, notably at the bi-annualLance Armstrong Foundation sum-mit. Rodriguez had a brain tumorbehind his eye at age 15 and asubsequent cancer on his tongue at26; despite a slight speech impair-ment, he’s an eloquent and tirelessadvocate for teen and young adultpatients and survivors.

Leukemia survivor AndrewMacKinlay, 15, whose motherCyndi serves on the pediatriccouncil, is also unafraid of thestage, speaking at various survivor-ship and fundraising events. “I tryand let people know that if I canget through cancer, they can too,and my mom talks about thethings a parent can do to help,”says Andrew.Many council members find the

transformation from private cancerpatient to public speaker to be verypowerful. “Who knew that I wouldbecome an advocate for cancerpatients worldwide?” said the lateScott Viera when his term as co-chair ended in Jan. 2007. “I havehad a chance to address a variety ofaudiences, from health care leadersto college students.”PFAC members are also leading

the way on the legislative front.Thanks to an idea from adult coun-cil member Anne Hristov, patientsand families can use a Web site tohelp influence cancer research andfunding legislation (see page 25).In addition, the council draws site

visits from hospital representativesaround the world, recently as far-flung as Iceland, who are lookingto study how the perspectives ofpatients and families are includedin patient care planning.

Personal growth, senseof communityGiving back. Making a difference.

Easing the next family’s cancer jour-ney. These reasons are often cited by“PFACers” for joining up. Once onboard, they frequently discoveranother benefit – personal growth.Many of the active or emeritus

adult council members (30 in total)

are cancer survivors, several yearspast treatment, and feel that takingpart helps them heal while theyhelp others. Those who are retiredor have a flexible work schedulecan attend meetings or work aspatient “rounders” in the clinics,gathering feedback from patientsabout their experience. Some evenmanage to serve during treatment;Dudley learned she had breast can-cer after joining the council as anine-year survivor of Hodgkin lym-phoma, and Viera was receivingcare for colon cancer while he wasco-chair. “Scott would go straightfrom his infusion chair to a meet-ing,” recalls Hayes.The councils also give members a

ready community of support. In aplace that emphasizes cure and sur-vival, both groups welcome the par-ticipation of families that haveexperienced bereavement. Formeradult council co-chair Jim Stam losthis wife to cancer, and current pedi-atric co-chair Christine Reilly losther 5-year-old son. “We see ourlives not only in terms of what welost, but what we were given,”reflects Reilly, who published abrochure to guide friends of fami-lies whose children are facing theend of life.Pediatric council members (eight

active and four emeritus) often haveto balance raising children, working,and tending to the needs of theiryoung cancer patient or survivor.Some, such as Rodriguez, facedcancer themselves as kids, althoughmost are parents who bring a specialkind of fervor to their work.“I notice as co-chair of the pedi-

atric council that parents advocat-ing for their children can bemore passionate than patients

Leukemia patient and PFAC memberAnne Hristov reviews Yawkey Centerfor Cancer Care plans.

Helping patients support legislation that helps patients

PFACmembers became “advocates for advocacy”when they proposed a new way for patients andfamilies to support legislation related to cancer.

Launched this fall, Dana-Farber’s Legislative ActionNetwork (LAN) helps patients, families, and staff memberslearn about bills and laws that affect them, and identifiesways they can voice their support or opposition.Although the LAN will organize workshops and other

learning opportunities, its chief instrument is an interac-tive Web site that highlights potential legislation orfunding proposals that affect cancer patients. The sitefeatures current bills before the state and federallegislatures, such as a proposal for Medicare to coverthe treatment summaries and follow-up care plans need-ed by cancer survivors. Visitors can express their opin-ions online, make a phone call, send an e-mail, join arally, or even show up at their state capitol building togive testimony.The LAN’s goal is to provide visitors with the basics

of advocating for public policy initiatives that help peo-ple with cancer, and offer resources to help them getinvolved in whatever capacity they feel most comfort-able. “It’s important for people to understand that theydon’t need special training or a degree in political sci-ence,” says Anne Hristov, an attorney and member of


advocating for themselves,”explains Rodriguez. “Manyparents want to make specificimprovements to benefit theirown child or other families.”For many, that is an integral part

of why they serve on the council.Mike and Caroline Rider, whose5-year-old son, Charlie, is aleukemia patient, have two tangi-ble goals. Mike wants to help cre-ate a chart for families to tracktheir children’s medications, andCaroline is leading the effort toinstall lockers in the Jimmy FundClinic for families to store theirpossessions. “When you spend theday in the clinic with your sickchild and his or her healthy sib-lings, you have a lot of stuff –

coats, snacks, games, homework –especially in winter,” Carolineexplains. “Right now, we have todrag everything around.”Even with Charlie in treatment

and two older sons at home, theRiders make time for council meet-ings and related volunteer projects.“We don’t have deep pockets, so weare willing to give our time to repaythe place that saved our child’s life,”says Caroline.Both councils are occasionally

rocked by the deaths that inevitablyoccur among a community of can-cer patients and survivors. Lastyear, Jessie Doktor, a 12-year-oldleukemia patient and daughter of apediatric council alumna, passedaway, and the adult group lost Viera,

44, who brought his stamina as aformer wrestler to his many roles:husband, father of two youngdaughters, college coach, full-timeretail manager, and cancer patient.Despite their achievements, the

rotating members of the councilscontinually find new things to workon. “There can always be improve-ment,” says Hristov. “Just when youthink things are good enough, youshould question yourself.” As thePatient and Family AdvisoryCouncils celebrate their 10thanniversary, they will continue tospread the message of patient-cen-tered care so that others can havethe same success.To learn more, visit www.dana-

farber.org/pat/pfac.

the Adult Patient and Family Advisory Council (PFAC)of Dana-Farber/Brigham and Women’s Cancer Center.“All you need to get involved is your story, yourpersonal experience, and your commitment to fightingfor improvements in cancer care and funding.”The formation of the network is a striking example of

the powerful impact that the PFACs can have. “I wasfamiliar with the importance of legislative advocacythrough some other organizations such as the Leukemiaand Lymphoma Society, and felt that Dana-Farber shouldhave a mechanism for involving patients and families,”says Hristov. “It’s a way for them to make a difference ifthey are not in a position to give money or volunteer.”Hristov met with Anne Levine, Dana-Farber’s vice

president for External Affairs, who was open to the idea;she then wrote a proposal, teamed up with EricRodriguez from the pediatric PFAC, and the projectbegan to take shape as a joint effort from both councils.“When it comes to ensuring that programs, policies,

and funding are aimed at cancer prevention, treatment,research, and survivorship, the message is more powerfulwhen legislators and other policymakers hear from thosewho are directly affected,” says Levine.For more information on the LAN, visit www.dana-

farber.org/legislative-action-network.

In August 2007, Betsy Grant, a33-year-old marketing employeefrom Holliston, Mass., began to

experience worrisome symptoms.She described some of them –nausea, moodiness, and menstrualdisruptions – to her gynecologist,who suspected that Grant’s hor-mone levels were awry, possiblydue to a non-invasive and easilymanaged growth on her pituitarygland. A magnetic resonance imag-ing (MRI) scan revealed somethingfar more serious – a brain tumor.Neurosurgeons at Dana-Farber/

Brigham and Women’s CancerCenter (DF/BWCC) removed alozenge-sized tumor from the rightfrontal lobe of Grant’s brain, diag-

nosed the next week as a grade IIoligoastrocytoma – a brain tumorwith a tendency to recur. In thedays that followed, scientists atDana-Farber and Brigham andWomen’s Hospital (BWH) rana series of molecular tests, someof which were developed byDF/BWCC neuropathologist KeithLigon, MD, PhD, which showedthat some of Grant’s cells werepositive for OLIG2 and CD68 –both proteins used for molecularcancer diagnosis.Based on the clinical characteris-

tics of Grant’s tumor, DF/BWCConcologist Andrew Norden, MD,suggested trying an experimentaldrug called vorinostat, in addition to

a standard drug and radiation. Nordenhopes that vorinostat, which hasshown promise in treating some braintumors, will “silence” the action ofcertain enzymes that prod Grant’stumor cells to grow unchecked. Grantsays, “I’m happy to know that, if thismedication gets approved, it would notonly benefit me but other people, too.”

A vital partnershipWith such precisely targeted drugs,

Dana-Farber and BWH researchers areinching closer to the promise of per-sonalized medicine – tailoring cancertherapies to the genetic makeup ofindividual patients and their cancers.To be successful, personalizedmedicine requires

Different-colored chemical stainsapplied to thin slices of tissue showwhether cells are normal or cancerous.

Journeyto the Center

of Diagnosis

By Prashant Nair

Slices of brain tumor are “snap-frozen” bypathologist’s assistant Kristin Gill immediatelyafter surgical removal at BWH.

Samples from tumorsremoved by surgeonsembark on a journeythrough diagnostic andresearch labs.

collaboration between scientists andclinical investigators located in labsat Dana-Farber and BWH.To aid in that collaboration,

Edward J. Benz Jr., MD, presidentof DFCI, and Michael GimbroneJr., MD, chairman of the pathologydepartment at BWH, organized atask force on molecular pathologyto explore personalized medicinefor patients of DF/BWCC.“Most people are not aware of the

central role of pathology in catego-rizing tumors for treatment and inmonitoring response to drugs –processes that cut to the heart ofpersonalized cancer therapy,” saysDF/BWCC pathologist Massimo“Max” Loda, MD, who chairs thepathology task force with JaninaLongtine, MD, co-director of theBWH Center for AdvancedMolecular Diagnostics.“Thepathologist’s report lendscre-

dence to theoncologist’s treatmentdecision,”Lodaadds. “It’s avitalpartnership, right fromtheget-go.”Pathology is a branch of medi-

cine dedicated to the diagnosisof disease through the visual exam-ination of cells, tissues, organs,and organ systems. Pathologyservices for DF/BWCC patients areprovided through a lab at BWH.For research, Dana-Farber hasopened a new Dana-Farber/Brighamand Women’s Center for MolecularOncologic Pathology (CMOP),

directed by Loda; though located atDana-Farber, it is a joint venture.At CMOP, researchers Loda,

Ligon, Ronny Drapkin, MD, PhD,and Shuj Ogino, MD, PhD, are try-ing to shift the terrain in cancerdiagnosis from traditional visualmethods to sophisticated molecularanalyses. “The effort has far-reach-ing implications for virtually everyrealm of cancer treatment,” saysneuropathologist Ligon.

A tumor’s journeyPatients at DF/BWCC begin a

journey that may include surgery,chemotherapy, and radiation. Butfew know that a little piece of theircancer goes on its very own journey.Spring 2008. It’s late on a Friday

afternoon when a team of neurosur-geons removes a small section oftan-pink tumor from the rightfrontal lobe of a patient’s brain.Although the surgery is meticulous-ly calculated, the surgeons dependon the expertise of the attendingneuropathologist to ensure that thetissue they removed came from thetumor. They await the pathologist’sdiagnosis as the tissue is broughtfrom the operating room into asmall sideroom.This “frozen section room” is

abuzz with activity, like a commandcenter of residents hunched over

microscopes. Withinminutes, a patholo-

gist’s assistant snap-freezes thetumor, cuts a thin slice, and mountsit on a slide. The slide is then dippedin a series of glass beakers withdyes, an arrangement not unlike anartist’s palette. The dyes, hema-toxylin and eosin, stain differentcomponents of the tumor cells tomake them more visible for neu-ropathologist Rebecca Folkerth, MD.

Folkerth enters the room, glassesperched like a pince-nez, with herpathology resident in tow. She peersinto the microscope, looking forsigns of malignancy. Dense, blue-tinged blotches of tiny cell nucleireveal telltale signs of runaway celldivision. Blood vessels crisscrossthe tumor’s crinkled landscape,indicating its greed for nutrients.Folkerth diagnoses the tumor as alikely high-grade astrocytoma – anaggressive, recurrent brain tumor.The pronouncement is preliminary,but it serves the surgeons’ purpose;they remove the rest of the tumor,and the 58-year-old patient is laterinformed of the tentative diagnosis.Before the tumor can continue its

journey – to the histology room, tothe CMOP at Dana-Farber, and tothe molecular diagnostics lab atBrigham and Women’s – Folkerthsets aside most or all of the tissuefor overnight preparation in orderto make an official diagnosis.This process begins with Shakti

Ramkissoon, MD, PhD, a pathology

Pathology resident Shakti Ramkissoonof BWH places samples into con-tainers to be preserved.

Stained samples reveal toan experienced pathologistthe typical abnormalities ofcancer cells.

“The pathologist’s report lends credence to the oncologist’s treatment decision.It’s a vital partnership, right from the get-go.” — Massimo Loda, MD

Betsy Grant (right), who is taking an experimental drug to combat abrain tumor, enjoys the view with her mother, Barbie.

resident, who “fixes” the tumor bybathing it in formalin to ensure thatits features remain intact. He thenplaces bits in small plastic recepta-cles and loads them into a process-ing machine that dehydrates thetissue overnight.The next morning, technicians in

the histology room slice and stainthin sections before Folkerth and asmall group of residents and fel-lows gather to determine the typeand severity of the tumor. Folkerthscans the sections, detecting abnor-malities an untrained eye mightmiss. She notices a spike in celldensity, a sign of frenetic cell divi-sion, clumps of calcium typical ofcertain brain tumors, flecks of redspotting that indicate thickenedblood vessel walls, and branchingthickets of blood vessels wherethere should be only a few, ifany. Folkerth also detects signsof infiltration – tumor cells havediffused through the brain towreak even more havoc.A pathologist’s work, Folkerth

explains, is to describe in detailthe characteristics of every

sample, combine that descriptionwith knowledge, and decide whatadditional tests are needed toclinch the diagnosis. From thisfinal pathology report, the oncolo-gist discusses the findings andtreatment options with the pat-ient. Herein ends one leg of thetumor’s journey through the path-ologists’ workshop.A second part of the journey

began earlier, back in the frozensection room. If enough tissueis available, a tiny portion will besaved for researchers at Dana-Farber, where the scientists examinethe tissue for clues that mightguide treatment.

The research sideThe Center for Molecular

Oncologic Pathology is a veritablejungle of high-tech instruments,extending the length of the secondfloor of Dana-Farber’s Jimmy FundBuilding. “Our goal is to marryclinical pathology, currently used to

diagnose patients, with researchpathology performed at CMOP.That marriage is likely to shapethe future diagnosis and treatmentof cancer,” says Ligon, whopioneered the use of OLIG2 asa diagnostic indicator of braintumors. Today, the test is a compo-nent of clinical diagnosis formany DF/BWCC patients.Microscopes, array scanners,

laser devices, and cutting instru-ments compete for space in baysoccupied by technicians, postdoc-toral fellows, and graduate students.Matthew Theisen, a technician inLigon’s lab, cuts the tiny, buff-col-ored sample from the operatingroom into fine bits, some of whichhe grows in a nutrient-rich slurry.This mixture prods the tumor stemcells – a small group of perpetuallydividing cells purported to fuel thecancer – to grow into tiny spheresthat can be studied in the lab twoweeks later.At that time, Theisen looks for

molecular markers that definethe tumor. These markers includeEGFR, a growth-signaling proteinimplicated in many cancers;OLIG2, a marker for cancer stemcells; and KI67, a protein thatreveals accelerated cell division.Seen through the microscope,these proteins look like magnifiedleopard skin, and reveal theBWH pathologist Rebecca

Folkerth (center, in lab coat)interprets a stained brain slice.

Pathology researchers (l-r)Keith Ligon, Max Loda,and Matthew Theisen



tumor’s aggressiveness. Theisendetects signs of rampant cell divi-sion and cues suggesting how thatgrowth might be slowed or stopped.Other clues come from more

involved CMOP techniques, such asarray CGH (comparative genomichybridization), which singles outhyperactive and underperforminggenes. Tissue microarrays can beused to simultaneously probemultiple samples for cancer-indicat-ing proteins. Laser capturemicrodissection uses a focusedlaser beam to isolate suspicious

parts of the tumor and air-lift themonto a receptacle for further tests.

Beyond diagnosisCMOP scientists go beyond

molecular diagnosis to help informtreatment options. For example,they are developing techniques thatsabotage cancer genes to keeptumor growth in check. AhmedIdbaih, MD, PhD, a postdoc inLigon’s lab, uses molecules, calledsmall interfering RNAs (chemicalcousins of DNA), to switch off theproduction of proteins, called tran-scription factors, which are

thought to keep brain tumor stemcells from maturing into adultbrain cells. Blocking these factors,Idbaih surmises, will slam thebrakes on tumor growth in patients.Extending the effort to use the

data generated at the CMOP, ClaireSauvageot, PhD, a scientist in thelaboratory of neurobiologistCharles Stiles, PhD, tests drugsfrom pharmaceutical companies oncells grown in labs and in mice.“With glioblastoma, we know

some of the molecular defects thatcause the tumor cells to become

malignant, so we test small-mole-cule inhibitors against them,”Sauvageot says. Using the geneticclues gleaned from the analysesdone by Ligon’s group, Sauvageotdetermines whether the inhibitorsmight kill brain tumor cells of acertain genetic stripe. “That’s theidea of targeted therapeutics. If wesee something promising, we moveit rapidly to clinical trials forgliomas,” she says.Besides going to CMOP, the

sample also goes to the MolecularDiagnostics lab at BWH. Teststhere pinpoint genetic defects intumors, which might aid diagnosisand treatment decisions.

At the lab, a technique calledMGMT methylation analysis aimsto determine which patients mightbenefit from the cancer drugTemodar®. Jesse Ladner, a wiry,soft-spoken technologist, analyzesthe sample using a technique thatdistinguishes methylated DNA –which is attached to a chemicalmolecule known as a methyl group– from unmethylated DNA.Methylation of MGMT, a specificgene on the DNA, “silences” thatgene, which might allow Temodarto kill tumor cells effectively.

Having provided a wealth ofmolecular information to guidetreatment, the tumor’s journeyends here. But the mission ofthe task force on molecular pathol-ogy has just begun.“The pathologist is right at

the center of personalized medi-cine, and the task force is aimedat making sure we’re at theabsolute cutting edge of expertise,”says DFCI President Benz. As itseeks to develop custom-designedtreatments for cancer, the taskforce is already on its way to har-nessing pathology’s potential.

Making use of leads from CMOPstudies of brain tumors, ClaireSauvageot in Charles Stiles' lab istesting drugs targeted to moleculardefects in glioblastoma.

“The pathologist is right at the center of personalized medicine, and the task force isaimed at making sure we’re at the absolute cutting edge of expertise.”

— DFCI President Edward J. Benz Jr., MD


Cori Liptak, PhD, discovered herinterest in pediatric psychology fol-lowing a summer internship atColumbus Children’s Hospital inOhio. Her path eventually led toDana-Farber, where in 2002 shebegan a two-year fellowship inpediatric neuro-oncology. Liptakloved working with the patients andfamilies and became a full-timestaff member. Now one of the seniorpsychologists in the Division ofPediatric Psychosocial Services, shesees patients with many diseases,though she specializes in pediatricneuro-oncology and survivorshipissues. Her role is diverse and thedays sometimes unpredictable – justthe way she likes them. Liptak viewsher work with families as a privi-lege, establishing relationships withpatients and allowing them directinvolvement with the medical team.The multidisciplinary division,

made up of psychologists, socialworkers, resource specialists,and school liaison personnel, pro-vides a wide range of services andsupport to pediatric cancer patientsand their families. This includes playtherapy, behavioral therapy, such astechniques to manage pain and anxi-ety, parent guidance, school consul-tations, and communication with themedical teams at Dana-Farber andChildren’s Hospital Boston. The 27-person team is integral to the carepeople receive.The emotional support offered

through the division is available toall immediate family members. It

often includes parent guidance,helping parents maintain a routineat home, assessing how siblings areadjusting to the illness within thefamily, and helping parents managethe transitions between various hos-pital and clinic settings. Supportextends beyond the immediate fam-ily and includes the patient’s schoolteam and classmates. Here, Liptaktalks about the process a familygoes through when a child is diag-

nosed with cancer and the role of thepsychosocial clinician.

The minute a family hears thediagnosis ‘Your child has can-cer. Your child has a brain

tumor,’ their lives are irrevocablychanged. An enormous emotionalroller coaster begins that takes ondifferent meaning depending onwhere people are in the process: diag-nosis, treatment, or post-treatment.

Cori Liptak, PhD, discusses her multifaceted role as a child psychologistand some of the “tools of the trade“ that help her deliver care andsupport for her patients.

First Person: Cori Liptak, PhDPediatric Psychosocial Services

Edited by Dawn Stapleton

“


When a child is diagnosed, thefamily goes through different phas-es. They wonder, ‘How am I evergoing to get through this?’ Theydo, however, learn to manage. Inpediatrics, all families are assignedto a psychosocial clinician rightfrom the start to help them adjust tothe new routine. Here, we recognizethat the psychosocial care is criticalto support a family in addition tothe medical care.Some people don’t understand

what we do because we do so manydifferent things. We might be play-ing the card game Uno with apatient or helping him or her with adoll and medical kit. Play therapy isa proven research-based technique.There’s therapeutic value in it, andit provides opportunities to learnabout the patient, his or her behav-ior, and approach to social situa-tions. Playing also gives children alittle bit of control and encouragesthem to just be kids. It’s reassuringbecause they think, ‘If I can play,I’m okay.’For example, I work with a 10-

year-old girl who comes for weeklychemotherapy treatments. The pos-sibility for mood and anxiety strug-gles is always present because ofthe demands of the treatment, andthe weekly play therapy sessionscan be very helpful during thecourse of a lengthy treatment day.She loves art and decided that weneeded to make a portfolio of allthe projects that we work on. Thishas provided a means to documenther treatment journey and a vehicleto express her feelings about illness.For instance, we wrote a story abouta sick centipede, and it was a beau-tiful way for her to express herstruggles, needs, and worries. When

she is done with her treatment andwalks out of Dana-Farber with herportfolio, she has something thatwill serve as a reminder of the workthat she has done, the relationshipsformed, and how she can cope whenthings get difficult.

Behavioral interventions also playa role in helping children mastertheir situation medically. Sometimesthey aren’t sedated for difficult pro-cedures, and they need to sit still,and we help them to get through it.We can do work ahead of time tohelp them prepare so they under-stand what their job is throughoutthe course of the procedure. Theymight say, ‘Cori, I’m going to sitlike a statue right now.’Anytimeyou get to witness a child usingsomething you taught and be suc-cessful as a result, that’s rewarding.For instance, when I use medicalplay with a child and see him stopgiving the puppet lots of shots, andinstead hear him say, ‘We’re nowgoing to put on your magic cream.It’s numbing and you’re not goingto feel a thing. Don’t be scared!’I’m watching him evolve in his

ability to cope, and that transfersover into his real-life experience.There are other behavioral inter-

ventions that go beyond what hap-pens in the clinic. For example, achild who had been sleeping in hisown bed before he got sick may

all of a sudden want to sleep in hisparents’ bed. We help him workthrough that while encouragingfamilies to continue to set limits.Upholding family rules and expecta-tions is important; it encouragesthe child and family to have a regu-lar routine – because that’s what’sgoing to be most helpful for himand the family.We also address the complicated

emotions that come with goingthrough cancer treatment and han-dling side effects. And we give peo-ple an opportunity to talk aboutthem and permission to not be okayall the time. That can be difficult,especially for adolescents. Theirattitude can be, ‘I’ve got it together.I don’t need any help,’ but whengiven the permission to “not be sofine,” their walls come down, andyou’re able to learn what they really

Christopher Bartorelli, 11, beats Liptak 3 to 1 at a gamethat employs cognitive memory and function.


Survivorship and treatment completion poses its own set of challenges.

Liptak engages Shayla Oliveira, 4, in medical play before herchemotherapy treatment.

need that they haven’t been able toask for.One of the biggest challenges is

working with families around end-of-life issues. It is important thatpatients and families have someoneto talk to about difficult treatmentdecisions, as well as their hopes,fears, and wishes. This can be com-forting for families as they focus onwhatever time remains.I worked with one young woman

who had things she wanted to do

before she died, and we made a list:‘I want to go someplace with myfriends, finish my scrapbook, getmy room organized.’ It’s very sim-ple, but it opened up a conversationabout what was important to her.The list exercise also served as aconcrete reminder that she had achoice about what her time wasgoing to look like and provided herwith a focus of how to get what sheneeded. It’s special for family andfriends to know that they helped

her accomplish items on that list.That carries meaning for them nowthat she’s gone.Conversely, survivorship and

treatment completion poses its ownset of challenges. Brain tumor sur-vivors struggle with multiple med-ical, cognitive, and physical chal-lenges. These impact school, work,and friendships; many strugglesocially. To help meet some ofthese challenges, I’ve started a pro-gram called STEPS (SuccessThrough Education, PsychosocialSupport, and Socialization) thatholds a dinner once a month forbrain tumor survivors and theircaregivers. Patients know thatthey’re going to see people who arelike them and understand whatthey’re going through, which iswhat has made people come everymonth. As part of the program, wetook a group of brain tumor sur-vivors to Project Adventure, wherethey worked as a team to overcomechallenging tasks like climbing atree and walking across a wire. Onegirl who is legally blind wanted totry the task, and the group workedtogether to help her get up the lad-der and to the tree. They did thissolely with communication andabsolute trust, and it was successfulbecause they all really care for eachother. These are people who haveestablished friendships outside ofDana-Farber. Once you’ve seen apatient connect with another patientand be able to say, ‘I have a friendwho understands,’ the power of thattype of success goes beyond any-thing I can really describe.”

®

DANA-FARBER CANCER INSTITUTE ...

“Dedicated to discovery ... committed to care” is the mission of Dana-Farber

Cancer Institute (DFCI), described as one of the world’s premier cancer centers

by the National Cancer Institute. Founded in 1947 by Sidney Farber, MD,

Dana-Farber is renowned for its unique blend of basic and clinical research and

for using its discoveries to improve the treatment of adults and children with

cancer and related diseases. It is a founding member of the Dana-Farber/Harvard

Cancer Center – one of 41 nationally designated Comprehensive Cancer Centers.

A teaching affiliate of Harvard Medical School, Dana-Farber is also one of 20

federal Centers for AIDS Research in the United States, and is consistently

ranked one of the top cancer centers in the country by U.S.News &World Report.

In addition, it has also earned “Magnet” status for excellence in nursing.

Dana-Farber partners with Brigham and Women’s Hospital to deliver care for

adults with cancer through Dana-Farber/Brigham and Women’s Cancer Center.

It also has a longstanding alliance with Children’s Hospital Boston to care for

pediatric cancer patients through Dana-Farber/Children’s Hospital Cancer Care.

By bringing together the strengths of three world-class institutions, these partner-

ships provide an exceptional level of care for cancer patients and their families.

... AND THE JIMMY FUND

The Jimmy Fund supports the fight against cancer at Dana-Farber, helping to

raise both funds and the chances of survival for children and adults around the

world. Named to protect the anonymity of one of Dr. Sidney Farber’s young

patients, the Jimmy Fund was established in 1948 by the Variety Children’s

Charity of New England in conjunction with the Boston Braves baseball team.

Later adopted as the official cause of the Boston Red Sox, the Massachusetts

Chiefs of Police Association, and the annual Pan-Massachusetts Challenge bike-

a-thon, the Jimmy Fund is widely regarded as “New England’s favorite charity.”

Individual and corporate gifts, many of them collected through numerous

annual Jimmy Fund events, have helped the organization generate hundreds of

millions of dollars for cancer research and care at Dana-Farber over the decades.

Non-profit Org.U.S. PostageP A I D

Dana-FarberDana-Farber Cancer Institute44 Binney StreetBoston, MA 02115-6084(617) 632-4090www.dana-farber.org

A teaching affiliate ofHarvard Medical School

Produced by DFCI Communications Department10/08

In an impromptu news conference, 9-year-old Ryan Reardon, a Dana-Farber patient and Big Papi fan, talks about “thejersey” and his favorite team. The David Ortiz Red Sox jersey, which was recovered from underneath the new Yankeestadium, raised more than $175,000 for the Jimmy Fund.

Documents

OP Winter-Spring AR 2005 · Title: OP Winter-Spring AR 2005 Created Date: 10/8/2008 5:28:52 PM