ONCOLOGY Vol 19 No 4

Positron-emission tomography(PET)–computed tomography(CT) has added a new dimensionto the imaging of cancers andcombination PET-CT scanners are becomingincreasingly universal. Theuse of combination scanners has increasedrapidly over the past 2 years-industry estimates are that the majorityof PET units sold throughout the worldwill be combination PET-CT scanners-and the authors have providedtheir own clinical experience and areview of the literature. While there issubstantial literature on the clinicalutility of PET alone, the use of PETCTis relatively new. The authors suggestthere is incremental benefit tothe addition of structural information(ie, CT) obtained at the same time asthe functional PET imaging.

The Lynch syndrome (hereditary nonpolyposis colorectal cancer[HNPCC]), is the most common form of hereditary colorectal cancer(CRC), accounting for 2% to 7% of all CRC cases. The next most commonhereditary CRC syndrome is familial adenomatous polyposis (FAP),which accounts for less than 1% of all CRC. Lynch syndrome is ofcrucial clinical importance due to the fact that it predicts the lifetimerisk for CRC and a litany of extra-CRC cancers (of the endometrium,ovary, stomach, small bowel, hepatobiliary tract, upper uroepithelialtract, and brain) through assessment of a well-orchestrated family history.A Lynch syndrome diagnosis is almost certain when a mutation ina mismatch repair gene-most commonly MSH2, MLH1, or, to a lesserdegree, MSH6-is identified. Once diagnosed, the potential for significantreduction in cancer-related morbidity and mortality through highlytargeted surveillance may be profound. Particularly important iscolonoscopy initiated at an early age (ie, 25 years) and repeated annuallydue to accelerated carcinogenesis. In women, endometrial aspirationbiopsy and transvaginal ultrasound are important given the extraordinarilyhigh risk for endometrial and ovarian carcinoma. Thesecancer control strategies have a major impact on at-risk family membersonce they have been counseled and educated thoroughly aboutLynch syndrome’s natural history and their own hereditary cancer risk.

Combined-modality positronemissiontomography (PET)–computed tomography (CT) isbecoming the imaging method ofchoice for an increasing number ofoncology indications. The goal of thispaper is to review the evidence-basedliterature justifying PET-CT fusion.The best evidence comes from prospectivestudies of integrated PETCTscans compared to other methodsof acquiring images, with histopathologicconfirmation of disease presenceor absence. Unfortunately, veryfew studies provide this kind of data.Retrospective studies with similarcomparisons can be used to provideevidence favoring the use of integratedPET-CT scans in specific clinicalsituations. Also, inferential conclusionscan be drawn from studies whereclinical rather than pathologic dataare used to establish disease presenceor absence.

Recent technical advances leadingto the development of integratedpositron-emissiontomography (PET)–computed tomography(CT) have been a boon for oncologicimaging. Combining these twoimaging modalities into the same imagingunit has greatly simplified visualfusion of function (PET) andanatomic (CT) data. The popularityof this modality has resulted in over60% of all PET sales currently beingPET-CT units.

In this well-balanced overview, Dr.Blank and colleagues explore thecurrent status of clinical investigationinto a possible role for inhibitingthe activity of epidermal growthfactors as a management approach inpatients with ovarian cancer.

Drs. Thompson and Luger’spaper provides a comprehensivesurvey of issues surroundinghematopoietic stem celltransplantation (HSCT) in myelodysplasticsyndrome (MDS). Whilefinding much of value in the paper, Istrongly disagree with the authors’opinion that “it is clear that youngpatients with [human leukocyte antigen(HLA)]–identical siblings. . .should undergo allogeneic HSCT assoon as possible.” This view wouldseem to rest on two premises: first,that allogeneic HSCT is, as the authorscontend, the only therapy“shown to alter the natural history ofMDS,” and second, that results withallogeneic HSCT are sufficiently“good” that the procedure can be regardedas a fixed, standard elementof medical practice.

In many respects, Lynch syndromeserves as the paradigm of cancergenetic syndromes. It is relativelycommon and accounts for approximately3% to 5% of colorectal cancer cases.The genetic basis is clearly understood,and genetic testing is clinically availableand routinely incorporated intoclinical practice. Furthermore, the diagnosishas a profound impact on themanagement of individuals at risk, andinterventions have been shown tosubstantially reduce morbidity andmortality. These advances in our understandingare attributable, in largepart, to the seminal work of Dr. HenryLynch and his colleagues.[1-3]

Drs. Thompson and Luger have written a thoughtful and comprehensive review of the therapeutic options and issues facing physicians caring for patients with myelodysplastic syndrome (MDS). In our commentary, we would like to highlight and expand on several areas of their analysis.

Opioid rotation is now consideredstandard practice in themanagement of cancer pain.The rationale for the approach hasbeen well summarized by Estfan andcolleagues. Rotation should be viewedas one strategy among many to dealwith patients who demonstrate relativelypoor responsiveness to an opioid.[1] Application of well acceptedclinical guidelines for opioid administration,beginning with those originallypromulgated by the WorldHealth Organization,[1] emphasizethe need to individualize the opioiddose through a process of gradualdose titration, irrespective of the specificdrug. Most cancer patients attainan adequate balance betweenanalgesia and side effects, at leastinitially. Some, however, experiencetreatment-limiting toxicity, the sinequa non of “poor responsiveness.”This response reflects an outcome thatis related to a specific drug, route ofadministration, set of patient-relatedvariables, and time.

The Groupe d’Etude des Lymphomes de l’Adulte (GELA) has conductedseveral phase II and III studies in patients with aggressive lymphoma,diffuse large B-cell lymphoma (DLBCL), and T-cell lymphomasduring the past 20 years, in France and Belgium. These studieshave demonstrated that the outcome of patients with DLBCL may beimproved and that the standard CHOP (cyclophosphamide, doxorubicinHCl, vincristine [Oncovin], prednisone) regimen is not sufficient tocure a large number of patients. The first improvement was the demonstrationof superiority of a dose-dense and dose-intense regimen, ACVBP(doxorubicin [Adriamycin], cyclophosphamide, vindesine, bleomycin,prednisone). The second improvement was made in young patients withpoor-risk lymphoma by intensifying their treatment with high-dosetherapy and autotransplant. The third and most significant improvementwas in the results associated with the combination of rituximab(Rituxan) and chemotherapy. Current studies look at decreasing thenumber of patients truly refractory to chemotherapy, decreasing relapserate with rituximab maintenance, and finding an appropriate regimenfor patients with T-cell lymphoma.

The majority of patients with ovarian cancer, especially those whopresent with stages IIIC and IV, will relapse soon after completion ofplatinum-based induction treatment. It is imperative to find ways to improveand/or enhance the efficacy of induction and to prolong the durationof the first remission. The epidermal growth factor receptor (EGFR)family has been exploited, and currently, three agents that directly targetthis group of receptors are in use in the treatment of colorectal,non–small-cell lung and breast cancers. EGFR and HER2/neu areoverexpressed in a significant percentage of epithelial ovarian cancers.Thus, it would be reasonable to explore directly targeted therapyin ovarian cancer. Numerous investigational trials involving a varietyof EGFR inhibitors in ovarian cancer are ongoing. Our institution hasan active phase II clinical study that seeks to define the role of erlotinib(Tarceva) in potentiating first-line chemotherapy, and to determinewhether the drug offers a significant contribution as maintenancetherapy. It is hoped that data from these and other studies will helpinvestigators to understand more clearly the biology of ovarian cancerand to delineate the role of EGFR inhibitors in the management ofovarian cancer.

Supportive care remains the mainstay of therapy for patients withmyelodysplastic syndrome (MDS). Although allogeneic bone marrowtransplantation is the only known curative therapy for MDS, its risksmake this treatment prohibitive in many patients, who tend to be olderand have other medical problems. With advances in hematopoietic stemcell transplantation (HSCT), we can offer transplant to an increasingnumber of patients. It is, however, necessary to assess each patient andhis or her disease individually and evaluate prognostic factors, treatmentoptions, appropriateness of HSCT, and, if appropriate, type andtiming of HSCT. We will review the data on HSCT in MDS in order toexamine each of these issues and clarify the decision-making process.

The overall strategy for appropriatemanagement of cancerpain has been well described inalgorithms that are the result of cooperativeefforts by experts from manydisciplines and cancer centers withinNorth America.[1] Conceptually, theapproach to cancer pain is straightforward.The etiology of the pain mustbe evaluated rapidly, and importantaspects of the patient’s history andphysical examination that could influencetreatment approaches must beidentified. Therapeutic options availableto patients with cancer pain areextensive and, if properly applied, resultin prompt and excellent pain relieffor most patients.

Dr. Henry Lynch was one ofthe first to recognize the existenceof hereditary nonpolyposiscolorectal cancer (HNPCC).While a relatively small percentage offamilies have this cancer predispositionsyndrome, identification of individualsat risk is now standard of careand includes the potential for the preventionof colorectal cancer. Dr. Lynchand Jane Lynch have written a guidehighlighting key points for physiciansregarding the diagnosis, surveillance,and management of this disorder. Severalaspects of clinical care mentionedin the article are expanded upon here.

Opioid rotation involves changing from one opioid to another usingcorrect equianalgesic conversion techniques to achieve better analgesiaand/or fewer side effects. The strategy appears to work because ofsignificant interindividual variations in response to both analgesic activityand toxicity. Although there are many retrospective studies, fewprospective controlled trials of opioid rotation have been published.The practical and theoretical advantages of opioid rotation includeimproved analgesia, reduced side effects, cost reduction, and improvedcompliance. Disadvantages include problems related to inaccurate conversiontables, limited availability of certain opioid formulations, druginteractions, and the possibility of increased expense. Weighing theadvantages and disadvantages is essential prior to making a decisionabout opioid rotation selection.

Ovarian cancer is the deadliestof the gynecologic malignancies.Approximately threequartersof patients present with advanced-stage disease. With aggressivecytoreductive surgery followed byplatinum-based chemotherapy, mostpatients will achieve remission. Despitethis initially good response totreatment, most patients experiencerecurrence and ultimately die of theirdisease. Novel treatment strategies areneeded. Molecularly targeted therapiesoffer the promise of improvedefficacy with decreased toxicity. Inthis article, Drs. Stephanie Blank, RichardChang, and Franco Muggiapresent an excellent summary of thecurrent status of epidermal growth factorreceptor (EGFR) inhibitors in thetreatment of ovarian cancer. They describethe promise of these drugs aswell as some of the questions regardingthe best way to integrate theminto therapy for ovarian cancer.

The use of sequential therapeutictrials to determine the optimaldrug for a given patienthas become a standard strategy in painmanagement. We appreciate Estfanand colleagues’ thoughtful and practicalreview of the advantages and disadvantagesof opioid rotation in cancerpain management.[1] Their commentson the need for individualization ofopioid dose and ongoing monitoring,opioid choice in renal and liver insufficiency,compliance, and cost reductionare particularly important.