Tobacco Documents Online

3 "The role of the cancer centers in the prevention of occupational cancer diseases lies both in primary and secondary preventive steps," Englund said. "The active use of health records established during the normal medical procedures can serve as an effective tool in risk identification. In a similar fashion, the re- sults of preventive actions taken can be monitored. Although early cancer detect;on programs for most applications still have failed to show their value, cer- tain occupationally exposed subpopulations with a high risk might benefit and a cancer center would in such cases be well suited to supply the most advanced diagnostic facilities." s Findings at Roswell Park that teaching of breast self examination in that institution's prevention-de- tection center improved breast Jump detection skills over randomized control groups instnicted by other modalities. Annlouise Assaf reported that the study popula- tion consisted of 388 adult women participating in a randomized clinical trial of BSE training methods. Each woman returned to the clinic for a followup in- terview three months after her initial visit. BSE fre- quency was defined as the number of times per month that the woman reported practicing BSE in the three months following her initia! clinic visit. BSE technique was determined by having the inter- viewer observe and record the steps used by the women examining silicone breast models with simu- lated breast lumps of varying sizes. The number, lo- cation, and size of the breast lumps found by each woman was categorized as detection accuracy. Re- sults indicate that ability to find lumps of varying sizes in a breast model is more closely associated with BSE technique than with frequency of BSE practice. • A retrospective study reported by Condict Moore of Louisville indicating a significant survival advantage for squamous cell oral cancer patients whose treatment plan evolved from multiple modal- ity consultations vs. comparable patients whose treat- ment planning involved only a'single modality. "We often hear that the first treatment specialist has the best chance of curing the cancer patient," Moore said. "We feel this should be amended in to- day's multimodality therapy climate to read plan- ning from multiple modality treatment consultations before the first t:,atment offers the best ~itance of curing the patient. A study of a, homo€enous group of squamous cancers of the oral cavity forms the basis for this opinion. One hundred dn.i thirty-six mouth cancer patients were analyzed retrospectively. They fell into two groups: a) those whose treatment plan evolved from multiple modality consultations; b) those whose treatment plan arose from a single mo- dality. Analyzed for disease free survival by stage, a 20 percent advantage appeared for the group that has pretreatment multiple modality consultation. This re- sult seems to support in general the second opinion approach, while specifically supportirtg the concept that in head and neck cancer multiple pretreatment opinions, from different specialties, panicuarly sur- gery and radiotherapy, confer a real advantage." 0 A report on the role of the preventive medicine clinic at M.D. Anderson in carrying out clinical and ep'.demiologic studies of AIDS and Kaposi's sarcorna victims. "During the last two years an increase in Kaposi's sarcoma (KS) and opportunistic infections (Ol ~ has been reported," Guy Newell said. "These have since been found to be the sequellae uf a defect in cellular immunity now called AIDs. Although initial reports were among young homosexual males, other groups with differe.^.t lifestyles are being affected. We ha%e aiudied over ) 20 subjects who volunteered for our preventive medicine clinic. Workup includes complete medical history and physical by one of us (Newell or P.W.A. Manseli), complete immunologic evaluation (by Evan Hersh), plus virologic studies and a detailed personal and lifestyle qaestionnaire. Among this group, 20 percent have no disease or ~ubclinical dis- ease, and fully 80 percent have measurable immune cellular deficiency manifest by clinical prodrome (45 percent), prodrome plus Ol (25 percerit), and KS plt.s or minus 01 (10 percent). We have treated 15 cases of KS in 10 months. Suspected causes include viruses (CM, EBV, other herpes, retro, etc.); chemicals (ni- trites, marijuana, cocaine, etc.); common infections (1A1, hepatitis B, amoeba, etc.); multipie sexually transmitted diseases, and perhaps elements of sexual practices. The transmissability of the syndrome from person to person is not known, although suspected. The publie health and scientific implications of un- derstanding the causes are enormous." + An analysis of the American College of Surgeons' recent survey of breast cancer. Charles Smart reported that these data showed a reduction in the nun.ber of patients treated by radical surgery, an increase ic the reported use of the modified radical operation, and the apparent increase in five year survival of breast cancer patients between 197 2 and the 197ti sun•ey data. Smart also noted that with the ACOS hospital cancer approvals program, involving nearly 1.000 hospitals which treat 60 percent of all newly diag- nosed cancer patients in the U.S.. the organization is in a unique position to do research on cancer control. DCCP BOARD APPROVES CONCEPTS OF NE W GRANTS TOTALING $1.4 MILLION A YEAR The Board of Scientific Counselors of KCI's Div. of Cancer Cause & Prevention Iast week gave concept approval to new grant supported research with an es- imated 31.4 million in firs' year a~can3c and to neN% and recompeting contracts v:orth an estimated SF08.• 000 rn first ycar aµards. The Cancer Letter Vol. 9 tio. 7 / Page 3

P.O. Box 2370 Reston, Virginia 22090 Telephone 7t)3-6204$46„ CCOP REVIEW COMPLETED. ENOUGH GOOD APPLICATIONS IN FUNDING RANGE TO GET VIABLE PROGRAM STARTED The three ad hoc committees organiied to review the 191 Contmu- nity Clinical Oncology Program applications completed their work last week, wrapping up what probably was the most massive review job on a single grant progiam in the history of NIH. The result: There were enough good applications in the fundable range to get CCOP off the ground and make it a viable program. The precise number of CCOPs that viill be funded will not be known rntil NCI completes negotiations with the centers and cooperative groups involved as research bases on costs of that scrv7ce. Also still to (Continued 1o page 2) in Brief COMPREHENSIVE CENTERS "JEINEL IN CROWN" OF CANCER PROGRAM, DEVII A SAYS; BOUTWELL NEW NCAB MEMBER "COMPREHENSIVE CANCER centers are a jewel in the crown of the National Cancer Program," NCI Director Vincent DeVita said at the dedication of the $37 million Kenneth Norris Jr. Cancer Hospital & Research Institute of the Univ. of Southern California. The Norris is a nine story, 158,000 square foot structure which includes 60 beds for cancer patients on two floors, surgery suites, clinical laboratories, three floors of advanced research labs, an outpatient clinic, day hospital, facilities for diagnostic imaging and radiation oncology, and administra- tive headquarters of the USC Comprehensive Cancer Center. The facility was built with a $12 million construction grant from NCI and S25,milm lion in private funds, including $5 millAon from the Norris family. Ken- neth Norris is chairman of the hospital board and a USC trustee. .:. KENNETH OLDEN, associate director for research at Howard Univ. Cancer Center, has been promoted to deputy director. He replaces CARRIE HUNTER, who resigned both as deputy director and associate director for clinical activities. ELLIOTT PERLiN was named acting associate director for clinical activities. JACK WHITE is director of the center.... ROSWELL BOUTWELL, professor of oncology at McArdle Laboratory, tiniv. of Wisconsin, is the new member of the National Cancer Advisory Board. He will fill out the term of Gerald Wogan. who resigned last year: that term will expire in 1Q84.. .. DENIS PRAGER, an assistant director cif the White House Office of Science & TechnolG- Fy Policy who has been OSTP's representative on the National Cancer Advisory lioard, will he leaving his job soon. No replacement has heen announced.... NCI HAS STARTED recruiting a new chief of the Re- searc'i Contra: ts Branch, a GS 15 position. That job became vacant when James Graalman was reassigned, an action hc has formally ap- pealed. Candidates for the posttton, a supervisory contract specialist, will he ctmsidered from ar.ywl:zre in the country. Robert Namovret, N('1 deputy executive officer, has heed icting chief of the branch. Vol. 9 No. 7 Feb. 18, 1983 %?CoPVr.gn119637heCancer letter Inc. Subbcnpt,on E125vetr NOr1h Art1Crica $ 150 vear eisewnere DCCP Board Okays Concepts Of New Grants Totaling $1.4 Million Year .. . Page 3 Centers See Trend To Integrate Control Service With Science ...Page2 RFPs Available ,.,Page8

CCOP REVIEW: THE MONEY WILL RUN OUT BEFORE THE GOOD APPLICATIONS DO 1Coniinued from page 1) be negotiated are indirect costs. The amount required for research base and indirect costs will come out of the 510 millionNCI has earmarked for the entire progrant. with the remainder available as d;rect costs to participating CCOPs. Best jeues- now is that at least 40 to 50 CCOPS will be funded, more if research base costs can be held to a minimum. Another factor will be how many of the applications in the fundable range were from the larger groups with the bigger budgets. There may have been as many as 100 applications of saffrcient quality to merit support, but the $10 million probably will have been spent before that number, is reached. "We probably will run out of money before we run out of good applications," one NCl staff member said. Program staff in the Div. of Resources, Centers & Community Activities and staff of the Div, of Extra- mural Activities who managed the review were im- pressed by the zeal and conscientiousness of the ad hoc committee members. The threc committees were chaired by experienced hands- David Ahmann, Virgil Loeb and Charles Spurr-but many of the members were community physicians and hospital administra- tors who had never participated before in an NIH re- view. The cOmmittecs c.athered in Bethesda the evening of Feb. 9 for their final meeting, worked late Feb. 10, wrapped up the review Friday, Feb. 11 and were packed and ready to leave when the Washington area's worst snowstorm in historv left them ma- rooned in their hotel. Few were able to leave for at k.ast another 24 hours. Dorothy MacFarlane, executive secretary to the Cancer Clinical Investigation Review Committee, supervised the three ad hoc committees with the help of three former executive secretaries called out of re- tirement. MacFarlane and other DEA staff handled the monumental task of processing the 191 apphca- tions and all the paperwork involved, did it smoothly and kept the review on schedule. They now must write the summary statements which will go to the National Cancer Advisory Board in May. Robert Frelick, DRC CA project officer for C'COP, combed through the applications before the review and came up with this breakdown. which he pre- sented at the recent meeting of the Assn. of Amer• ican C anarer Institutes: There were 1,652 components- hospitals and physician offices-in the 191 applications. 541 of them hospitals. Fort%•-nine applications had one com- ronent, 94 had two, 36 had from frve to 10, and 10 had more than 10. Three were statewide consortia. 'There wrre more than 1,01?0 Physiciim particira• ting, including 2,400 medical oncologists. Some ap- plications listed radiotherapists and surgeons as prin- cipal investigators. The average medical school graduation date for participating physicians was 1965, "which reinforces our assumption that now we have enough well trained young oncologists to carry out this program," Frelick said. Participating hospitals have a total of 197;000 beds and see 330,000 new cancer patients a year, a signif- ican )onion of the 800,000 plus in the U.S. diag- nosed each year with cancer. Seventeen cooperative groups were listed as re• search bases, some by only one applicant and one by 61 applicants. Thirty centers were listed as rr'search bases, with from one to 10 applicants each. The proj- ected number of protocol cases that would be avail- able for studies totaled 22,000. "I have the impression that if the p,ogram slopped tomonow, we would already have improved commu- nications bet wecn the communities and the centers;" Frelick said. "What about the research bases themselves? What if they received 5,000 plus new patients a year from the program? Do they have the staff capable of handling that many and monitoring them' WWe asked for estimated costs in the applications. The response was from zero dollars to over 51,200 per case. "Some CCOPs had very sophis:icated data manage- ment plans; others seemed not to know what we were talking about." On the issue bf quaiity control, Frelick said that DRCCA staff will make annual site visits to each CCOP and research base. "We anticipate that institu- tional review boards will be in order. Initially, no CC'OP will be funded without an operational IRB. We will ask research bases for an annual report and their own evaluation of the status of members." TREND SEEN IN CENTERS TO INTEGRATE CANCER CONTROL SCIENCE WITH SERVICE Cancer control researchers from 25 cancer centers participated in the "Progress in Cancer Control" con- ference held recently in Bethesda, the third such meeting coordinated by the Assn. of American Cancer lnstitutes, the Assn. of Community Cancer Centers, and Roswell Park Memorial Institute. Focus of this meeting was on cancer control re- search activities in centers. Curtis Mettlin, conference organizer, said the proceedings "reflected the trend in cancer centers to integrate science with service in their cancer conRrol activities." Presentations at the meeting included: • A report from Anders Englund, executi%c direc- tor of the Intrmational Union At:ainst Cancer f IrICCI. on a demonstration of the inter3cuon of cancer institules and national data bases in S%+•eden in monttortng cancer nsl.c in the workplace. The Cancer Letter Paye 21 F eb. 1$, 1983

an apparent excess of cancer deaths among his fellow workers Subsequent eprdemiologsc snvesuFottons of pattern makers noted a tv:ofold excess of colorectal cancer. In response to these frn3rngs, the Pattern Makers League (PAfL),1Sorkers In- su.utC for Safet,y and Health (11'I), and ernplovers of Fattera makers initiated a cancer screening and educational program. B% lle:ember 1983 approximately 80 percent of the 10,60 roembers of t,tc PhlLare expected ta have completed the initial screening examinzvons, which mclude physical examrnauons (pnmanly, deargned to identify colon cancers and colvn poay ps), medual hrstones, and selLadmmstered questionnaires covering dret. occaratton, and tobacco and alcohol use. The physical examnatron includes a rectal exan and srgmoidoscopy, stool grraiac test, complete blood coun., urrnalysrs. lung ;~nction ±csts, and chest x•rays. Results from these tests are made available to the PML member and hts/her personal physician. Data from this comprehensire screening program p,Fovide an opportunity to investigate the role of occupational, dretiry. and other factors tn the origin of colorectal cancer and polyps. A study of colorectal polyps would be vaboahle for several reasons. First, it is widely belreved that polyps, partietnlarly, adenomatous polyp,, are precancerous lesions. Histopathologic characteristics provide the strongest evidence. although adena matous polyps and colorectal cancer are also statistically as- soci.ated with regard to geographic distribution, socioeconoim ic level, and ume trends. Second, if polyps are precancerom, lesions, then the time between first exposure to dietary, occu- pational, or other factors and appearance of polups w-ill be Im t),an the latent period for development of cancer. This may enhance our ability to identify and quantify poorly un• derstood risk factors for colorectal cancer. Finally, mmst persons with pciyosare asymptomanc and are less hkely to have modified thur dietary habits because of the lesion or therapy than are persons with cancer.'iherefore, serum levels of mrcronutnenas and subject recall are less likely to have been affected. This may counter one of the major metjtologrc Froblems of case control surdrn. We anticipate that the nurn- bPr of cases of cplon cancer will be quite small. However, to tile extent possible vre will compate charactensttcs of persons with colon cancer and colon polyps to determine whether or not the two diseases share srmrlar etiologies. A case control study is planned. Cases will consist of all patrem makers diagnosed with colorect,l cincer or polyps through the WI screening program. Smcc women and minor. itones account for less than five percent of the PA1L member• shrp, most caseti are expected to be white men. In preliminary srrcenrng resu'r. from Detrott, the pre.atence of polyps was 18 percent. It tlie prevalence ofpulyps in other areas to be Fcreened were ssSnslar, approximately 1,400 polyp cases would he rJentdicd. The prevalence from Detroit is higher than eom• nwr,ly encowilered and we will rnvesLFate whether or not this may be dae to a rigorous examination that identified small lesions. Six cases of colon cancer were uncovered among the 1,:00 pattern makers screened in Detroit, a aumber that was unusually htgh. Controls will be PF1L members w4thout colorectal disease, matched one to :ne to the cases of race, sea, and clinic of exammanon. AssummE an alpha level of.05 With 10 percent of the nrnehsea,Pd pnpubuon e~pnsed to a causal factor, a study of 1,400 pol.p cases and an equal number of comrols .vculd he able to detcct a rmnintum odds ratio of 1.5 mth 90 percent powet. while a study of 700 polyp cases w-uld be able to detect a mrmmum odds ratto of l.7 with a power of 00 percent. A twv staee approach rs planned. In the fsrst stage, data celL lected b% N'I dunng screening will he anah•7ed to determure the pre-alence ot poh•ps (by age. anatomic locat on. sve. hts- topitLoloFsc fe.ttures) among patrern makers Questtonnaue data on occupational. dretary, and other factors will be com- pared an.ong cases and cnntrols toevaluate the role of these factors in ihe origin of polyps. A pathology review and tn- dustrral hygrene evaluanon of workplace exposures will occur in this stage also. Slides or blocks of tissue from a sample of polyps %%tll be obtau•.ed lot a pathology revtew. If the dtag- noses by the revrewmg patholoFists agree •aith those of the submitting pathhlogists, no additional review will take place; otherwtse aJ ull revtew of 311 cases may be required. All risk factor analyses onll be related to spectfic histopathologic charactensucs of these polyps. To obtain addtuonal mforma• lion on workplace exposures and to validate exposure infor- mauon obtained from pattern makers, we plan to conduct "walk through" surveys of a sample of pattern making shops. In the second stage, we w7il supplement the screening data by obtaining- on a sample of the cases and controlt, more comprehensive tirformatron on occupational exposures and dietary pat terns, and by taking blood samples to determine 3erurn levels for Lpids, vitamin A.,vitamin C, vitamin E, caru- pene, selenium. zinc, ard copper. It has been hypothesized that these mrcro~tutnents are assoaated with colon cancer in humans, but further clanficatron is needed. There is essen- trally no evidence, however. regarding the role of these factors in the origin of colorectal polyps. The contract covered by this concept is for collection and analysis of blood drawn from a sample of the cases and con• trols. The specific cases and controls sampled for these deter- minations will be based on the rtsults of the questsonnane and pathology analyses in stage 1. The Wl has recently initiated a second round of screening in some geographic repons of the co6.itr 1. For effcrency and cost containment, we will attempt to re-ontact cases and controls during t hss second screen. Surlport for this project will come from several sources. In general. screening and all aspects of the oricrnal data collectron is supported by the 111, a•hrle supplemental data collectron on the cases and controls will be supported by NCI. The 117 recesves support frcro several sources including NCI. The NCI support wil1 be through professional senrce procurenrents, exisnnp support service contracts, and new contracts. The major "new" funding from \CI %~il1 be for serum nucronu- tnent analyses. Board member Hilary Koprowski suggested that an eff'ori be added to the program to find some anti- gens that might be predictive of cancer of the gastro- intestinal tract. Joseph Fraumeni, director of the Field Studies d Statistics Program, agreed. Koprow- ski also suggested that "with itse of innovative histo- chemistry, you might find out v.hich polyps may turn into cancer and w hich not." Aaron Blair, proiect officer, agreed. Omenn noted that access to occupational popala- tions frequently is d:f.`ycult. This proposal, in v% )t.rch DCCP by "pi€gy backing onto the NV1 study,. ...+711 be getting a high rate of partt,:tpation. The suggc•stion by Hilan• is extremely important." The concept was approved, with the proviston that some Board members be arpointed to ,rdsrse DtY'P on the second phase of the study. lm-entory of union records systems. CMe year, S I'(r,000. Narsattve : In order to carn out tt, responsibthtses, the tndustrrwidc Studies Branch (ItfSBr ef XIOS)l must he able to rdennfy and ch3ractenze worker populattons eapcn°d to aFent, themg considered for eptdennological n,.estugatuon. ' 4non reonrd s.% stems ;pe;trton funds and f`cnefit p!a^• ) can rr,,% rde 'rhe Cancer Letter Pags 6/ Feb. 18, 1983

portant rccent work dcmonatrates that several natural rn;rrhrtors sut+press carcinogenesrs in the rrornoUon rh,,+c. .,. wcll as their better known acti•:iUes as hlr, t,lI1L 'Jgt'nts before and c'unng initiation.) Fur- jhermore, ascotbic acid and tocopherol act to inhibit both the in vitro and the in vivo formation of car- 4rnogcns. That these compounds have the possibility of being intnnsically nontoxic is also most significant. Some knowledge exists concerning mechanisms of action of these compounds with respect to effects on the activation of car.:mogen metabolism and the in- ic studies of a,protective effect, such as the green and yellow vegetables. The I3oard agreed t;r Adamson's suggestion to table the proposal until the ;\tay trieeting. \vtth a workshop to be convened in the ardterim to consider research needs in natural rnhibitors. R FPs AVAI LABLE Requests /or prdposal described here pertain to conuaces planned for award by the National Cancer fnstttute unless otherwisenoted. Write to the Contracting Olbccr or Conrracr Special/stlor copres of the RFP, citrng,the RFP number, h'Cl duction of :]etoxrfying pathways, and there is sonie hsrings willshow the phone number of the ContrdctmgO/• knowledge of dose and schedule considerations as lrcer or Contract Speuafist who will respond to questronss these relate to Antineoplaslic effects. Address requests forNCl RFP< to the in'rirvidualnamed- the "All of this knowtedge, however, is at a most hldr- B!air building room numbershovvnf Natipnal Cancer Institute, 8300 Colesville Rd., Silver Spnng, VNd. 209W RFP announce mentary level• and most importantly, the full range mentslrom othe'ragencies reported here vvillinclude thecom• of inhibiting substances present in foods, and their p/ere mailing address at the end ofeacho interactrons, is virtually unexplored temtory. Such RFP NIH-ES-83•8 knowledge is of critical importance not only from the standpoint of experimental chemoprevention of Title: Test forchenricallr irrduced transposition in carcinogenesis. but also relative to the epidemiology drosoplrila of cancer prevention in dietary/nutritional studies. Deadline: Approximately April15 It is crucially important to expand studies on natural 7fbe National Toxicology Program, National In- inhibitors of carcinogenesis in a broad spectrum of stitute of Enviionmental Health Sciences (NIEHS), is a:eas tn.luding the :dcntifrcatron, t~olation, puriGca- soliciting quahGied sources harir.g the capability to lion and charactenzahon of preventive compounds, de\rlop a rapid screen methodology to detect chem- the.r mechanis,ns of actton, assays for their rdentific- ically induced gene transpositions in drosophila mel- atron, thcir preparation or synthesis in quantity, anogaster. Offerorsshould possess demonstrated pro- their pharmacologtcal'loxicoloPtcal properties, the frciency and expetience in drosophila genetics and conditions under \vhich inhibition is demonstrable, molecular clening techniques• the carcinogens, rocarcinogrns, and/or promoters RFP NIH-ES•83•7 against \s~hich inhibition or suppressio~t is demon strable and the spc.•trum of tuniors against w•luch ac- Title: Drosophila nruta,genesis tt•sting ti\ rty is seen. The obiccuve :,t the proposed Ri=A is Deadline: Appmximatelr april 8 to stimulate furlhcr research in these areas ti•tth The National Toxicology Progrdm is soliciting qual- special reference to natural inhihitors of carL:inogeh- ified sources ha\irrg the capabihty to perform droso• esis." phila sea•linked recessive lethal and heritable trans- Board member Pelayo Correa commented that it lo:ation assays for detection of mutagenic and poten- has becn the consensus of workshops that the corre- tially carcinogenic chemicals The successful contrac- lation oi frun; and \egetables to the inhibition of tors shall each be required to test approxrmately 80 cancer has been better than that of vitamrns them- chemicals over a four y'ear period for mutagernrrtt selves. Edward Bresnick suggested that selenium and using the sex-hnked recessive lethal test and, if neLes- vitamin A precurscrs not hc included in the RFA, sary, the reir{^roral translo.ation test in drosot hrla since thcy alrrady are being eatenstvely atudred. Ad,rmson said that the SI million could fund as m.Lny as eight grants tf they are close to the NIH awrag-? of about S 120.000 a year for ROls. Board mernbcr C.C-. Cheng said. "1 wonder if four I ears i5 cnough? Perhaps we could have smaller grants. for a longer timc." Board member Allan Connev said that the focus should be on foods \srth e\idence from eprdemto!og- melanog.astcr (7fferors should possess dcmenstrated proficiency and e-%penenco in the uw of dro"Nphllj for detection of chemrcalh• induced mut,rtions Above t\vo RFPs: National Institute of Emironmental llealth Sciences, Procurement Office Attn: Hollis J. )la\shins P.O. Box 12874 Research Triangle Park. N•C. 277:1Q The Cancer Letfe r_ Editor Jerry D. Boyd F,,L.~.nP„ ip' tY:• .• 3~e3t 111 r hP Leile'. h. • P : Nt`. ...70. n. \'.•,1--: <,9n A x, vL':'- snr ,'1 T n,r Ct I -c.,t C.)nt r• Let:fY :111 •PW.s[R' Cr It`C „ , ' C" 1•- 1`ul .-r , r rtl,s lt^ •f;. -w7iCntt . -(V 'l 'IC^' O• V3••1•-• anl . . 1c'r•r.ctL.tA^- mr.v.c,,•-Pv,,^n.C n,. . ~,a C`otc,cC, .r•• , : t•in.. . ~ ,.tr' ,. •- . .. , r M • .. .. . , . • I' . .1 . .

NV"o7I5314 One of the new grant programs is designed to stim- ulate viroAogical studies of acquired immunodeficien- cy disease syndrome, at a cost of $1 millron a year. The $iological Carcinogenesis Branch of DCCP preDosed to issue a request for applications to solicit R01 grant applications in virology/AIDS research. The Board's motion to approve, offered by Gilbert O+nenn, directs that the awards be in the form of coopera4ive ag.reements, to permit greater DCCP staff participation; asks that the National Institute of Al- 1ergy & Infectious Diseases be brought into the proj- cct; and asks that safety officials from NIH and the Centers for Disease Control be consulted on btocon- tainrnent. The staff narrative justifying the RFA: Acqurrcd immunodeficiency syndrom (AIDS) is a new dis• ease u•h,ch was f rst reported in 1981. There are now over 950 documented cases. Although first rep.uted in promiscious homusexyal males, the AIDS disease now includes both homo- sexual and h;,sexual males, heterosecual intravenous drug users, hemophilia patients. Haitians, some infants, and apparently nonrial here'rose'tuals of both sexes. In addition to disorders of rmmunologrQal funcuon, apprbximately half of the AIDS vic• t,ms suffel from pneumocystr3 cannir pneumonia and about one•r hrrd of them have Kaposi's sarcoma (KS) or lymphornas. The morrality rate is near 40 percent overall, but closer to 85 percent for cases diagnosed eatly on in 1981. The long term progrlosts rot frank cases is very poor. The recerit involvement of hemophiliacs. apparently normal children. and some common epidemiological features now sug• gest a bluod borne• venereal, or close contact transmissible b,olopcai agent as the causative factor. Two vrruses. human cyto?iegalovuus (IiCf•1V) and Epstern•Barr virus ('rBV). have already bebn linked with AIDS. KS. and lymphomas. Human cytomegaCovrrus has oeen associated with KS by at least one molecularly onented study of KS tissue, and Epstein-Barr Vrrus determined nuclear antigen has been demonsrrated in tissues of jeveral AIDS patients wath a Burkttt's•hke lympho- ma. Several viruses have already been assocsated with certarn human cancers. There is the etiological assocratton of EBV to nasopharyhgeal carcrnoma; the wart viruses with mahgnancres of the skm.cenoc and anus, HOSV wrth l:S;human T•cell leukcrma•lyur`homa vrrus (HAV) with several malignancies; and the recn,c advances in the study of cellular and viral onco• genes relauve ru cancer ,nduction. All these advances mdreate iha, ahere r,•.ruunal basis for rnrtranng s~stemau: efforts to cear.•h fc• rnc trensnussrble agent responsible for the AIDS s%ndrome. The pur:,ose of this RFA is to snmulate studies aimed at a direct vuolrpcal approach to the problem. 11 rs designed to encaurage 3tudies on the search for, the isolation. and the charactenzation of the viral agent(s) which may be the pn- mary causative factor in AIDS and KS. The studres proposed should encompars not only the classical virological methods of t,zsue culture. animal inoculation and serolog}. but also the contemporary• technolopes of viral tmmunology, c,. togenetucs• and n,olecalar biology. Since HCDI\' and EBV, buth trans• formn,F vtrusos, have been nnplicated in immune suppressrrm and rn association with KS and l%mphomas. •9cfimrne studies of fiCN1V aTrd EBV and their relationship to .41DS ar:d KS I ma, he omsr~iered as perunent to the obtecn.es of tite RFA. Hosve\ er. pVotects tnvolvtngerther or both R\A•core or D!%A• eore vrruses ate encouragcd E\amples of,he types of studres that might be,appropnate rncluder 1) drrect in vi.o and in v• tr ef forts ar rsolatron, rdcnbfrcatron and charactenzat,on of the causatrvr f arucular virus. : 1 analys:s of human trssue u rrl: ahprrpnate te,sts rndu:aUoc of tlt: rresence. state of mrerra• The Cancer Letter Page 4 1 Feb. 18, 1 583 lion, and chrornosomal location of viral or pro-viral DNA. 3) recognition and identification of marker antigens of pathog- nomomc stgnrficance; 4) cytogeneuc analysis for chromo- somal changes that relate to disease rnducuon; and 5) in mro search for direct morphological transformation of appropnate target cells. Because of thr changing nature of AIDS and the importance of prevention of the syr.drome, applications for researi:h on the development of an appropriate vaccrne would also be welcomed should a vrral agent be rderiufied in the interval between initiation of this RFA and the time for re• cerpt of applications. Board member 119arcel Baluda pointed out that there are now no "clear cut guidelines for biocon- tainnient.l'm concerned about possibly funding some amateurish applications. I think we should in- sist on controls, be specific, and not leave it up to the individual investigators." "Details on planning for containment should be in the RFA," Nicholas Petrakis satd. Myron Essex sug- gested that CDC's expertise in biocontainment could be tapped. DCCP Director RicharJ Adamson commented that NCl has been expect;ng traditional RO1 to study the relationship of viruses to AIDS, "but they ha%e not come in." Program Director Jack Gruber said that at present, there is only one such RO1 in all of NIH. He said he hoped to be able to fund as many as six or eight grants from the RFA. but that depends on the nature and quality of applications. NCI will set aside $1 mil,hon to fund the giants in the first year, if enough high quality applications are submitted. The Board agreed to expand an RFA it had ap- proved last September with an earmark of S{00,000 in first year funding to S900.000. That money .vould support researcl: in hepatitis B virus and primary hep- atocellular carcinoma and biological tnvestiFations of virus host interactions and mechanisms and causation of human cancer. The need for the addilional estimated S400.000 developed when, in writing the RFA. staff felt the program could be expanded to include a model sys- tem, cell culture, and possible chemrcal involvement in the etiology of the disease. Balt6da said that witlt. the development of a vacctne against HBV, `the solution ,rtay be in sitht:' and suggested that is %ehy there are onl3• two current RO Is 1n tl'JS area. E•ssex said he disagreed that the vaccine vsill elim- inatc 11BV "in the foreseeable future. It is a latent virus, and the cost of the vaccine is high." Board Chairman Peter Magee suggested another aspect of the problem, that afflatoxin ma% be im- plicated in the etioleFy of the drsease. The Board approved the expansiorn unaninmously. Staff narrative: Currentl, t , eprdcrnro+>pcal rn.esnFatrons bnk hepatius B virus tnfe:tuons with pnmarn hepatocellular carcinoma in man T7us hnkaFe uas discussed at an NO ;onicrenrc on hepamts B%rrus ahd prunarn herato:ellular carc,mo,na hcl ; rm 11ar ?-a. IQS_. The cons.•n±u+ oi thr attendec, at il:at mecun;, uas

v3luable infonnation when searclung for appropnate study populations. Hawever, there has never been an inventory of these record systems whrch documents and categonzes exist• ing data. As an example of exrsting datt sources, the lnter• national Foundatron cf Employee Benefit Plans (IFEBP) has a membership in excess of 4,000 benefit prog•ams, the major• ity of which are sponsored by the AFLCICI. The intent of this Proposed project rs to support a contract in developing an m• ventory of union data and specifically to: 1. Identify by name, address, and contact individual, the vanous menibeh programs selected for the inventory., 2. Contact these programs and document pertinent infor• mation that wou!d be useful in epidemiologic research, such as a description of the benPfit program; size of the program, extent of information induded in records, the time period covered by the program, and occupations or exposures that may be represecrted by the program. 3. This inventory of data will be delivered to N10SH and NCI in a readily accessible form, e.g., computer tape or Wang diskette and the data will be made avaibable to other research- era in the community at large. Survey of campounds which have been tested for carcino- Renie activity. Tlus contract, presently held by Technical Re• sources Inc., will cost an estimated 3285,000 in FY 1983. It will be recompeted for the 1984-86 fiscal years, with an es- umated cost of 5288,000 in 1984. hruiative: This project and concept was presented to the Board of Scientific Counselors on Sept. 30, 1982, The survey, which has been published by PHS6NCI since 1951, covers a search of relevant journals(600•700 worldwide'r, reports, m, ono- graphs, and books in several languages. Appropriate data are extracttd, indexed and assembled in abstract form. The cur- rent concept covers extension of prepaiatton and publication of this report for the years FY 84, FY 85 and FY 86,. The prior years are ip preparation and process of publication. The Board gave approval of this concept for one year (FY 1984) with the proviso that a user survey be conducted to determine the effectiveness and needs for this report and whether currenA users would want these vo?umes if tt,tey had to purchase them. The Board requested that the results of this survey be brought back to the Board meeting in February at which time extension of the concept atld funding for FY 85 and FY 86 wouid be contemplated. Results of the survey were predictable: Most of those contacted said they needed the survey and relied on it; very few said they would pay for it. Adamson said that NCI could not on its own reqttire payment for a geverrtment publication, that only the Supt. of Docr.tments (Government Printing Office) could do that. The Board agreed to drop the idea. The Board gave concept apprrval to the following noncompetitive contracts: • Procurement of human blood platelets, two years, estimated cost S60,000 a year. with Commu- nity Blood A. Plasma Service, Birmingham, Ala. This company already has a contract with NIH to supply blood products to the clinical center. DCCP needs human blood platelets for research in Laboratory of Chemopreverition. • Application of Epstein-Barr virus markers to diagnosis and prognosis of NPC and occult tumors of the nasopharynx i.n the U.S., estimated cost $175; 000 a year for two years. This is a two year extension of a contract with the Atavo -linic. • Radiation dosimetry for epidentiological studies, estimated cost S75,000 a year, five years. Ttus will be a collaborative research interagency project with the Food & Drug Administration. NCI's contribution represents only a small part of the total cost. • Followup sQudy of women evaluated for infertil- ity, estimated cost $ 100,000 a year for two years. This is an extension of a coniract with the Afa_vo Clmlc. • Retrospective cohort mortality study. This is the project totally funded by the Air Force for a mortality study of civilian employees at Hill A;r Force Base. The pro* iect originally was approved in 1981 and started in FY 1982 and is now being cY• panded. The existing contract with Westat for sup- port services is being expanded from $606,000 to $901,000. The project also includes small contracts with the General Services Administration and the Mormon Church. The Board postponed a decision on an RFA for experimental, studies on natural inhibitors of carcino- genesis, with an estimated cost of $1 million a year for four years, when some members felt that the proposal as preso:nted was aimed at active research areas which shot.tld not need further stimulation. "1 find this unattractive," Omenn said. "I don't believe you can cite inactivity. There are many such studies. I'm flabbergasted by this proposal." The staff narrative written to justify the proposal listed a number of items that have been studied in animals as natural inhibitors bf carcinogenesis .+nich exist in food-various vegetables, fmits and seeds, and, recently, powdered green coffee beans, black tea leaves, and cocoa. "The purified compounds (inhibitors) known to exist in food represent a chemically diverse set: or- gartic isothiocyanates and thiocyanates, phenols, coumarins, terpenoid compouads, flavonoids, and indoles," the narrative said. "Vitamins C and E, and the vitamin A precursor, (3-carotene, and selenium, known inhibitots of carcinogenesis, are of course con- stituents of foods. Macromolecular proteast• inhibit- ors such as exist in legumes which inhibit or n•tard the carcinogenic prc;.ess, ar: also just beginning to be purified and studied. Finally, various sources and types of dietary fiber such as wheat bran and citrus pulp a•e kno%sn naturai inhibiturs in eaperirncntal carcinugenesis. "Anticarcinogenir, constitthents in foods. and thr foods themselves, have ::nl.noun potenttal for the inhibition of cancer,in man. 1: should be emphasrze3 that the studies performed to date tndre,rte that these inhibitors are widespread in nature, of Frrat chermcA dtversity, and are btrlocicalh• effective in reducing cancer incidence a:7d'or tumor burdcn in se-eril species of experim-cntal animals, many organ sttes. against se eral cateFones of chemical carcinogens. and at cereral staee+ of the carcmoFenic proce- tl:n The Cancer L.eLt:e r Vol. 9 No. 7 / Page 7

that hepatrtn B virus was the best model rn humans of a spec- ific agent related to a speciirc cancer. In addition it was felt that there was a lack of understanding of the broloBcal mech- arisms for the diseases processesattributed to hepatitis B virus and that all of these mechanrsms ifre worthy of further mvestrgatron. The intent of this RFA would be to encourage research to determine: (a) whether or not hepautts B vrrus is a complete carcinogen in humans; (b) the molecular mechanrsms under- lying the interaction of the virus wjth hepatocytes in human and animal model systems; (c) the characteristics of model systems already developed in terms of their suitability for studying the development of hepatocellular carcinoma and establishing their relevance, if any, to human disease; (d) the gene products of the hepatitis B virus in terms of their func- tion and whether any of the gene products are transforming proteins. The following representative research is projected: (I) studies to determine whether or not the hepatitis B virus rs a complete carcinogen in cultured , human liver cells or in animal model systems; (a irvestiptuons on the mechanism(s) of c.ncogenests by IfBV mcludmg tne role of integratec JNA in transformation, examination of virus coded proteins for trans- forming potential and development of im vitro model systems for transfotmatron; (3) studte; on the progression of acute hepatitis through chronic hepatitis to pnmary hepatocellulsr carcinoma, including studies on why tumors develop in only a limited number of individuals infected with the hpeatitis B virus (possible host determinants of the process) and on the mechanism(s) by wlrich chromc infecttons are rnamtained in the immunologically competent f,rost; (4) studies on the cyto- pathology of the disease to shed light on the mechanism of liver damage. e.g., to deterriune whether virus replicatron, naural killer cells, cytotoxu T cells or other mechanisms might be involved. These studies should provide the biological equivalent of tae very strong epidemiologic evidence which now links hepatitis B virus to primary hepatocellular carcinoma in man and should also provide objective criteria for the evaluation of present and future vaccuies wiuch may be useful in the pre- ventron ot this disease. The Board approved the following competitive contract concepts: Cancer risk in women irradiated for benign gynecological disorders. Three years, estimated total cost 5300,000 per year for multiple aw rds. The narrative: Studies of populations exposed to ionizing radiation are conducted by the NCI epidemiology program to strengthen the quantitative basis for risk estrhtatron, to improve under- standing of the role of host and eitvrronmentai factors that in- fluence the dependence of cancer nsk upon dose, and to pto- vrde tnsrF)us into carcinogenic mechanisms. Between 1930- 1960 rt was not uncommon for women xith endometrial by- perplasta and other benign gynecological drsoders (BGU) to have their ovaries irradiated to control dysfunctional uterine bleedrng. An investigation of such women treated with mtra- caciary radium, external beam x-ray, or both will provide risk estnnates for cancer of pelvic and abdortunal organs, sttes that ;tave not been wel'. charaacnred for radiation nsks,at dose levels n:uch lower than those received by cervical cancer pa- uents under studN b%. odt prvgram. Further, any n.sk of radio- genic leukemia in BGD will be compared a tth the rather low risk associated with much htFher exposures in cenical cancer patients The unexpectcd teductton in breast cancer nsk pre- vwush• assucrated uith radia uon for BGD in Wumen past the age of inenopat.te uill be also evaluated as well as any modif rcatton of risk by host factors. Ther studx s~dl mvesnFa:e the dependence of can.er risk on vanatrvn in dosc, rachatuun u:rahtl, and aFe at ex(+Onute. TLIs study shoulo provide dosrmetnc data for evaluating excess cancers of pelvic and abdornmal organs and thus pronde ac- curate nsk estimates for sues where little information exuts. Unique dostmetry resources developed under our program are available. This study should also help to clanfy the paradoxic- al finding of increased leukemia nsk associated with low dose CONCEPT REVIEW FIGURES ARE ESTIMATES ONLY; RFPs, RFAs NOT YET AVAILABLE The doilar estimates with each concept review brought before the various boards of scientific coun- selorc are not intended to represent maximum or exact amounts which will be spent on those projects. They are intended only as guides for board members to help in determining the value of the projects in relation to resources available to the entire program or division. Responses should be based on the work- scope and description of goals and methods included in the RFPs (contracts) and RFAs (grants and coop- erative agreements). Availability of RFPs and RFAs will be announced when the Institute is ready to re- lease them. but not high dose exposures to the pelvic bone marrow, and thus may provide furth.er insight into the mechanism of radta- tton leukemogenesis. Objective: T o determine cancer incidence and mortality arqd estimate the risks of radiation-mduced cancer in women treated for BGD. Methods: A study size of at least 6.000 exposed women should be suffrcrenr to provide adequate statistical power to detect ard evaluate dose-tesponse relauocshrps for iadrncenic leukemia and solid tumors. Therapy usually involved 600-800 rads to the ovaries, and bone marrow doses have been esttm- ated to range between 70•190 rads. Estimates to other organs range between 25-n00 rads. Out existing dostmetry program for cervical cancer can be adapted to estrmate organ doses for this study It is estimated that approxrmately 30 excess leul.- emtas will be observed and 220 excess cancers of heavily u- radtated srtes such as the uterus and colon. Women irradiated between 19341960 would be included for study. rurrently, NCI is collaborating with the Karolinska 11os- prtal, Sweden, in a study of 1,000 exposed and 1500 non• exposed women treated for BGD. An additiona15000 exposed women have been identified in New Yotk, Atassachusetts, and Connecticut. We anticipate issuing a competime RFP, and will consider multiple awards; Medical, therapeutic, and followup information would be abstracted from medical records. Death certificates would be obtatned for those who died. and questionnaires sent to those lcoated alive. binnahty analyses will be made, and we are also planning comp3nsons with Connecticut populatton rates of cancer incidence, and with women treated Nnhout radiation for BGF- if a large enough cohort of unxposed uomen can be assemhled. Or fan specific radratton doses uill he detemuned for indi,idual 8GD patients Case control study of colorectat polyps amone pattern makers. Lstimated total cost, 2lou,D00 per year, two years Pattern makers construct prototypes for mass produced items such as automohrtes, acncultural equtpment, and nther products. The% may work wilh wood, metal, and pidsnc and rnay, therefore, come in contact with wood dusts. metal dusts. plastic furr,es. epoxv restr.s, suhrnts, cutting urls, and paints Cvncem over adserse health effects from these exposures atase in 1Q7F µhen a pattern maker notified his union ah-u; The Cancer Letter Vo1. 9 No. 7/ Page 5