ONCOLOGY Vol 19 No 1

As outlined by Dr. Ruckdeschel,the evaluation and management of metastatic spinal metastasesand associated epidural spinalcord compression have been simplifiedby the advent of magnetic resonanceimaging (MRI), which is muchmore sensitive and specific than plainx-rays and radionuclide bone scanning.Furthermore, because most patientscan now undergo MRI ratherthan invasive myelography, thethreshold for diagnosing epiduralmetastatic disease has been lowered.Accordingly, it has become the test ofchoice for evaluating most patientswith suspected spinal metastases.

The use of hormonal therapy with external-beam radiation (EBRT)to treat prostate cancer is a topic that has been well explored. The potentialuse of hormonal therapy and brachytherapy in the treatment ofprostate cancer, however, continues to be controversial. This review isbased on our current interpretation of the available literature assessingthe outcomes of patients treated with EBRT and brachytherapy withor without hormonal therapy. Extrapolating from the findings of theRadiation Therapy Oncology Group (RTOG) 9413 trial, there appearsto be a favorable interaction between hormonal therapy and irradiationin the lymph nodes. The benefits demonstrated with whole-pelvicEBRT and hormonal therapy are likely to extend to patients treatedwith brachytherapy as well. Studies suggest that the role of hormonaltherapy in brachytherapy is limited without the application of wholepelvicEBRT due to the inability of brachytherapy to address potentiallymph nodes at risk. The potential role of hormonal therapy in conjunctionwith brachytherapy without pelvic radiotherapy, is limited byinconclusive data and abbreviated follow-up times.

Drs. Andrews and Roach present an excellent review and discussion of the existing literature regarding the role of androgen ablation therapy in patients being treated with external-beam radiation therapy (EBRT) and prostate brachytherapy. However, the indications for, and optimal timing of androgen ablation with radiation therapy remain controversial, particularly in regard to brachytherapy.

Vaccines are a promising but still experimental treatment for melanoma.They are intended to stimulate immune responses against melanomaand by so doing, increase resistance against and slow the progressionof this cancer. Key requirements for vaccines to be effectiveare that they contain antigens that can stimulate tumor-protective immuneresponses and that some of these antigens are present on thetumor to be treated. Unfortunately, these antigens are still not known.To circumvent this problem, polyvalent vaccines can be constructedcontaining a broad array of melanoma-associated antigens. Severalstrategies are available to construct such polyvalent vaccines; each hasadvantages and disadvantages. Clinical trials have shown that vaccinesare safe to use and have much less toxicity than current therapy formelanoma. Vaccines can stimulate both antibody and T-cell responsesagainst melanoma, with the type of response induced, its frequency,and its magnitude depending on the vaccine and the adjuvant agentused. A growing body of evidence suggests that vaccines can be clinicallyeffective. This evidence includes correlations between vaccineinducedantibody or T-cell responses and improved clinical outcome,clearance of melanoma markers from the circulation, improved survivalcompared to historical controls, and most convincingly, two randomizedtrials in which the recurrence-free survival of vaccine-treatedpatients was significantly longer than that of control groups.

There have been an astoundingnumber of published reviewson human cancer vaccines, andI take responsibility for my share. Apparentlythe interest of the medicalcommunity in cancer vaccines remainsintense, despite the modest progressthat has been made in our field and thepaucity of convincing, positive clinicalresults. Somehow the idea of treatinga cancer by inducing an antitumorimmune response or strengthening theexisting one is strongly appealing bothto physicians and to patients. Whetherthis enthusiasm is justified by the scienceis a question that should troublethe sleep of all of us who call ourselvestumor immunologists.

Drs. Bystryn and Reynoldspresent an overview of melanomavaccines, including atheoretical rationale to support the approach,criteria for an effective vaccine,and a discussion of the challengesto optimal vaccine design. Results ofclinical trials where vaccine-inducedimmune responses correlated withimproved clinical outcome are discussed,as well as limitations of monitoringvaccine-induced immuneresponses. A series of randomized, concurrentlycontrolled trials with complex,polyvalent whole-cell vaccines,extracts, lysates, or shed antigens arereviewed. The authors conclude thatmelanoma vaccines' "potentially mostsignificant application" may be the preventionof melanoma in individuals athigh risk of developing the disease.Their review discusses the generallyaccepted rationale for selecting vaccineantigens and does a thoughtfuljob of reviewing the current state ofcomplex melanoma vaccines.

Several key areas must be considered in the diagnosis and managementof spinal cord compression. Because the outcome can be devastating,a diagnosis must be made early and treatment initiated promptly.Although any malignancy can metastasize to the spine, clinicians shouldbe aware that this occurs more commonly in certain diseases, ie, lungcancer, breast cancer, prostate cancer, and myeloma. The current algorithmfor early diagnosis of spinal cord compression involves neurologicassessment and magnetic resonance imaging of the entire spine.Treatment generally consists of intravenous dexamethasone followedby oral dosing. Depending on the extent of the metastases, symptomsmay also be managed with nonnarcotic pain medicines, anti-inflammatorymedications, and/or bisphosphonates, with local radiation administeredas needed. Surgery has often led to destabilization of the spine.

In this issue of ONCOLOGY, Dr.Ruckdeschel addresses a subjectthat, fortunately, is not very common,but unfortunately for those inwhom the problem occurs, the outcomesare almost universally poor.The subject is probably one of themost dreaded complications of advancedcancer-malignant spinalcord compression. On a positive note,since Dr. Patchell's plenary sessionpresentation at the 2003 AmericanSociety of Clinical Oncology Annualmeeting,[1] interest in metastatic spinalcord compression has been renewedand there is hope that futurepatients with this problem will farebetter.

Icommend the authors for their excellent review and discussion regarding the integration of hormonal therapy with permanent prostate implants. They address several important issues relating to the sequence and duration of hormonal therapy in combination with externalbeam radiation therapy (EBRT) and its underlying relationships with permanent prostate implants.