ONCOLOGY Vol 17 No 1

Venous thromboembolic disease is a common but likely underdiagnosedcondition in the cancer patient population. Timely and accuratediagnosis of venous thromboembolism is imperative due to the unacceptablemorbidity and mortality associated with a misdiagnosis.Because diagnosis of the condition based on clinical grounds alone isunreliable, physicians should select an appropriate objective diagnostictest to confirm or refute their clinical impressions. Compressionduplex ultrasound is the best initial imaging test for both suspectedupper- and lower-extremity deep venous thrombosis. Magnetic resonancevenography (MRV) is a valid alternative when ultrasound isinconclusive, but contrast venography remains the “gold standard.”Suspected pulmonary embolism should be initially evaluated by helical(spiral) computed tomography (CT) or ventilation/perfusion lungscintigraphy, the former being preferred in cases of obvious pulmonaryor pleural disease. Indeterminate studies should prompt performanceof contrast pulmonary angiography. Inferior vena cava thrombosis isalso best assessed by contrast venography, with MRV and CT reservedas alternative imaging modalities. Evidence to date suggests thatD-dimer assays remain unreliable in excluding venous thromboembolismin cancer patients. A newer latex agglutination D-dimer assay mayprove to be clinically useful in this setting.

Erectile dysfunction is a common sequela following potentiallycurative local treatment for early-stage carcinoma of the prostategland. With larger studies and longer follow-up, it is clear that erectiledysfunction following prostate brachytherapy is more common thanpreviously reported, with a myriad of previously unrecognized sexualsymptoms. Approximately 50% of patients develop erectile dysfunctionwithin 5 years of implantation. Several factors including preimplantpotency, patient age, the use of supplemental external-beam irradiation,radiation dose to the prostate gland, radiation dose to the bulb ofthe penis, and diabetes mellitus appear to exacerbate brachytherapyrelatederectile dysfunction. The majority of patients with brachytherapy-induced erectile dysfunction respond favorably to sildenafil citrate(Viagra). Despite reports questioning the potency-sparing advantageassociated with brachytherapy, recent elucidations of brachytherapyrelatederectile dysfunction may result in refinement of treatmenttechniques, an increased likelihood of potency preservation, andultimately, improved quality of life.

Drs. Basche and Kelly presentan excellent comprehensivereview of the treatment ofnon–small-cell lung cancer in olderpersons. Articles such as this, whichfocus on the older patient, are of paramountimportance for several reasons.First, cancer is a disease ofaging, with an 11-fold increased incidenceand a 16-fold increase in cancer-related mortality among patientsover age 65 compared to those under65.[1] Second, the population is aging,and in the year 2030, approximately22% will be over 65.[1] Third,data on older cancer patients are limitedsecondary to an underrepresentationof this population in clinicaltrials.[2,3] Based on these facts, acomprehensive review of the availabledata is important, especially toguide future research.

Financial costs to individuals andsociety represent one measureof the burden of disease. Accurateand complete estimates of thefinancial burden associated with cancerare a necessary component forreaching a variety of goals. Thesegoals might include the costs andbenefits of cancer control interventions,assessing the performance ofhealth systems, and the allocation ofhealth-care and research resourcesacross disease categories.[1]

Champlin and colleagues haveelegantly summarized the conceptof nonmyeloablativestem cell transplantation (NST),stressing the importance of this newlyemerging procedure for the treatmentof patients with life-threateningmalignant hematologic and nonhematologicdiseases. This review doesnot include a description of the safetyand efficacy of NST for the treatmentof many life-threateningnonmalignant diseases for which noalternative therapy exists. This categoryencompasses a long list of geneticdisorders, diseases caused by adeficiency of stem cell products, andsyndromes associated with immunedeficiency. However, discussion ofthese illnesses is beyond the scopeof this review, which focuses oncancer.

The Northwestern University Costs of Cancer Program consists ofa series of pilot studies that address the costs of cancer care. Theprogram is designed to serve as a template in preparation for undertakinga large-scale study of a nationally representative sample of cancerpatients-ie, in preparation for a cancer costs and services utilizationstudy in the future. In this article, we outline the theoretical frameworkassociated with a study of cancer costs and summarize findings fromour ongoing pilot studies in this area.

This article by Marcelo Gomes,MD, and Steven Deitcher, MD,is a well conducted, thorough,and scholarly review of the diagnosticmethods for venous thromboembolismin cancer patients. The authorshave specifically looked at upperandlower-extremity deep venousthrombosis (DVT), pulmonary embolism,and rarer conditions includingthrombosis of the inferior venacava (IVC), pelvic veins, and eventhe portal vein. They offer descriptionsof the various tests available,address the pros and cons of thosetests, and provide the reader with algorithmsfor the diagnosis of DVT andpulmonary embolism, including twofor pulmonary embolism-one basedon ventilation/perfusion (V/Q) scanningand one based on helical computedtomography (CT) scanning.

The article by Drs. Merrick,Wallner, and Butler providesan excellent overview of issuespertaining to sexual dysfunctionfollowing prostate brachytherapy.The authors were the first to addressthe historical and current problemswith diagnosing sexual dysfunction.They make a strong case for developinga quality-of-life (QOL) instrumentthat is specific for prostatebrachytherapy.

During the past 5 years, manyexciting clinical observationsabout nonmyeloablative allogeneicstem cell transplantation(alloNST) have been accumulating.The shift from the successful demonstrationof mixed chimerism in largeanimal models to the clinical utilizationof alloNST has been unusuallyrapid. According to the recent InternationalBone Marrow TransplantRegistry analysis, 1,390 alloNSTtransplants have been registered since1996 in North America, 92% of thembetween 1999 and 2001, with datafor the years 2000 and 2001 still incomplete.

The importance of cancer as aproblem in the elderly is gainingincreasing appreciationdue, in part, to the demographicchanges taking place in this countryand around the world and their associationto the incidence of cancer.Ongoing epidemiologic research overthe past several decades has consistentlyconfirmed the continuing trendtoward an aging population. In theUnited States, an anticipated 20.1%of the population will be 65 years ofage or older by 2030, the number ofpeople 75 years of age or older willhave tripled, and the 85-or-older agegroup will have doubled.[1]

Longitudinal cohort studies ofspecific populations providesome of the most compellingevidence for research spanning epidemiology,medicine, and social science.The Framingham Heart Study(FHS) is a good example. Initiated in1948, the FHS tracks a cohort of whitemen and women who reside in thetown of Framingham, Massachusetts.The study population receives biennialmedical exams and personal interviews,and an additional study hasfollowed their offspring. The FHShas contributed much of our knowledgeabout cardiovascular disease incidenceand prevalence, and its riskfactors.

The majority of individuals diagnosed with lung cancer in theUnited States are 70 years of age and older. Defining appropriatetherapy for older patients with non–small-cell lung cancer (NSCLC) isbecoming a major focus of clinical research. In this article, we reviewthe available data on clinical predictors of risk and benefit for elderlyNSCLC patients receiving treatment via a variety of modalities, includingsurgery, radiotherapy, combined radiotherapy and chemotherapy,and chemotherapy alone. The data demonstrate that subgroups ofelderly patients benefit from appropriately selected treatment. Participationof older patients in clinical trials designed to assess efficacy,toxicity, and quality-of-life outcomes for recently developed treatmentmodalities in this population is critical.

President Bush has proposed policy changes to restrict the abilityof drug companies to extend their patents past their expirationdate. Mr. Bush said current federal laws and regulations try tobalance the goals of innovation and accessibility.

The diagnosis of venous thromboembolismon the basis ofclinical signs and symptoms isnotoriously inaccurate and, therefore,mandates confirmatory diagnostictesting. Unfortunately, all diagnostictests for deep venous thrombosis(DVT) and pulmonary embolismhave clinical or practical limitations.Contrast venography and pulmonaryarteriography are usually regarded asthe reference standards for the diagnosisof DVT and pulmonary embolism,respectively. However, evencontrast venography may be impossibleto perform in 9% to 14% ofpatients, may fail to visualize 10% to30% of venous segments, and maybe associated with postvenographythrombosis in up to 8% of patients.[1]

Afederal court has invalidated the US Food and Drug Administration’s“Pediatric Rule” after concluding that its requirement thatdrug companies test the safety of adult drugs in children is contraryto the intent of Congress. Judge Henry H. Kennedy, Jr, of the US DistrictCourt for the District of Columbia, enjoined the FDA from enforcing theregulation. He found that the rule exceeded the wording of laws passed byCongress that provide specific incentives to the pharmaceutical industry toestablish the safety of new and approved drugs in pediatric patients. TheFDA can appeal Judge Kennedy’s ruling to the Circuit Court of Appeals.

Over the past decade, prostatebrachytherapy has been usedincreasingly as definitivetreatment for early-stage carcinomaof the prostate gland, with the majorityof the literature on brachytherapyreporting biochemical results as favorableas those in the most positiveradical prostatectomy and externalbeamradiation therapy series.[1-4]Because of a lack of definitive evidencesupporting the efficacy of onelocal treatment approach over another,quality-of-life (QOL) parametershave assumed greater importance. Ithas been widely asserted that preservationof potency is more likely followingbrachytherapy, but longerfollow-up has raised substantialdoubts about brachytherapy’s potency-sparing advantage.[5,6] In addition,brachytherapy results in amyriad of previously unrecognizedeffects on sexual function.[7,8]

The current ONCOLOGY articleby Drs. Merrick, Wallner,and Butler is a valuable additionto the literature. An estimated189,000 American men were diagnosedwith prostate cancer in 2002,and 30,200 died of the disease, makingit the most common cancer amongmen, and the second most commoncause of cancer death.[1] The treatmentshave led to a high rate of cure,but the results of treatment oftencause a reduction in quality of life.

This article nicely describes concernsabout the underdiagnosisof deep vein thrombosis(DVT) and superficial vein thrombosisin patients with malignancy. Theincidence of these conditions in thissetting has been demonstrated to beas high as 51% in postmortem studies,as opposed to the clinically recognized15% rate. The articlereinforces the need for better diagnostictools than are currently availablein clinical practice. It alsostresses the need for a high clinicalsuspicion. Duplex ultrasound shouldbe used as a first step, and othermodalities listed in the article needto be used when appropriate.

High-dose myeloablative therapy with allogeneic hematopoietictransplantation is an effective treatment for hematologic malignancies,but this approach is associated with a high risk of complications.The use of relatively nontoxic, nonmyeloablative, or reduced-intensitypreparative regimens still allows engraftment and the generation ofgraft-vs-malignancy effects, is potentially curative for susceptiblemalignancies, and reduces the risk of treatment-related morbidity.Two general strategies along these lines have emerged, based on theuse of (1) immunosuppressive chemotherapeutic drugs, usually apurine analog in combination with an alkylating agent, and (2) lowdosetotal body irradiation, alone or in combination with fludarabine(Fludara).